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CANCER 


ITS    NATURE,   CAUSES,    DIAGNOSIS 
AND  TREATMENT 


ROBERT  HOLMES  GREENE,  A.M.,  M.D.,  F.A.C.S. 

EMERITUS  PROFESSOR  OP  SURGERY,  MEDICAL  DEPARTMENT  OP 
FORDHAM  UNIVERSITY,  ETC. 


PUBLISHED   BY 


JAMES    T.   DOUGHERTY 
409  West  59th  Street  New  York  City 

1918 


COPTEIGHT,   1918 
BT 

ROBERT  HOLMES  GREENE 


PREFACE 

The  views  expressed  in  this  volume  are 
the  results  of  the  labors  of  a  surgeon  and  a 
physiological  chemist,  working  together  for 
the  past  few  years.  The  chemical  work  has 
been  done  by  John  A.  Killian,  Ph.D.,  Patho- 
logical Chemist  at  the  House  of  Calvary  for 
Cancer,  and  formerly  Instructor  in  Physio- 
logical Chemistry  at  Fordham  University. 
No  attempt  has  been  made  to  settle  definitely 
many  of  the  questions  arising  in  connection 
with  this  wide-spreading  disease,  but  an  effort 
has  been  made  to  show  the  lines  along  which 
future  investigators  probably  must  work.  In 
addition,  the  result  of  the  labors  of  the  au- 
thors is  presented,  both  as  to  methods  of 
diagnosis  which  they  have  found  useful,  and 
as  to  principles  and  details  of  treatment,  the 
carrying  out  of  which  may  ameliorate  some 
of  the  suffering  and  at  least  often  retard  fur- 
ther progress  for  a  considerable  length  of 
time. 

We  wish  to  thank  the  following  individu- 
als for  valuable  aid  rendered  us  in  the  prep- 


PREFACE 

aration  of  this  volume,  for  suggestions,  aid 
given  in  obtaining  manuscripts,  as  well  as  for 
the  carrying  on  of  investigations^  which  have 
both  directly  and  indirectly  resulted  in  this 
production:  Drs.  E.  W.  Caldwell,  H.  H. 
Janeway,  J.  H.  Larkin,  L.  Fetzer,  Ph.D., 
Max  Kahn,  Douglas  Quick,  and  R.  J.  E. 
Scott;  also  Mr.  J.  S.  Brownne,  N.  Y.  Acad- 
emy of  Medicine;  Rev.  Walter  Dwight,  S.  J., 
Rev.  John  J.  Wynn,  S.  J.,  Mrs.  Marie 
Killian,  Mr.  Louis  Pine,  Mr.  Louis  Protz- 
mann,  Mrs.  L.  Smith,  and  Mr.  E.  C.  Stein- 
ach,  Ph.G. 

Robert  Holmes  Greene, 
78  East  56th  Street,  New  York  City. 

June  I,  1918. 


CONTENTS 


Part  I.     CAUSES  OF  CANCER 

CHAPTER  PAGE 

I.  Etiology  of  Cancer 9 

II.  Heredity 23 

Part  II.     NATURE  OF  CANCER 

I.  Nature  of  Cancer    30 

II.  Precancerous  Conditions 54 

Part  III.     DIAGNOSIS  OF  CANCER 

I.  Details  of  Methods  of  Sulphur  Findings  in 

the  Blood  and  Urine  60 

II.  Diagnosis  by  Chemical  and  Bacteriological 

Means 72 

III.  Diagnosis  of  Malignancies  of  the  Stomach.  .     81 

IV.  Differential  Diagnosis  between  Epithelioma, 

Syphilis,  and  Diseases  of  the  Skin 90 

V.  Diagnosis  by  X-Ray  and  Cystoscope    95 

VI.  General   Consideration  of  the  Condition  of 

the  Blood,  Hair,  Nails  and  Saliva 107 

Part  IV.    TREATMENT  OF  CANCER 

I.  Basis  of  all  Successful  Treatment  to  be  Found 
in    Measures    Which    Tend    to    Increase 

Tissue   Metamorphosis 112 

II.  Vanadium  and  Arsenic.     Iron  and  Mangan- 
ese.   Condurango,  and  Other  Bitter  Tonics  121 

III.  Radium,  and  X-Ray 132 

IV.  Excision    139 

V.  Selenium  and  Tellurium 144 

VI.  Preparations  for  Cleansing,  Deodorizing,  and 

Disinfecting  Cancerous  Lesions  of  the  Skin  157 

VII.  General  Considerations    168 


PART  I 
CAUSES  OF  CANCER 

CHAPTER  I 

Etiology  of  Cancer 

In  the  whole  field  of  pathology  there  is  no 
problem  at  once  more  essential  and  more 
baffling  than  the  disclosure  of  the  causes  in- 
citing and  promoting  the  growth  of  tumors 
of  all  kinds.  The  question  of  the  origin  of 
the  unchecked  proliferation  of  cells  and  the 
transmission  of  the  resulting  neoplasms  to 
foreign  hosts  has  occupied  the  minds  of  ex- 
perimentalists and  clinicians  as  well  for  cen- 
turies, and  although  a  number  of  ephemeral 
theories  have  been  proposed,  at  the  present 
day  we  are  as  ignorant  of  the  etiology  of  can- 
cer as  we  were  when  the  study  first  began. 
It  is  to  be  lamented  that  many  investigators, 
far  from  adding  to  our  knowledge  upon  this 
subject,  rather  have  introduced  confusion 
by  the  invention  of  new  nomenclatures  and 

9 


lO  CANCER 

the  adoption  of  complicated  classifications. 
However,  it  is  not  our  purpose  to  enter  into 
a  lengthy  philosophical  discussion  or  specu- 
lation upon  fantastic  theories  of  tumor  etiol- 
ogy, but  rather  as  a  working  basis  for  the 
clinicians  to  point  out  the  salient  features  in 
our  conception  of  the  cancer  process  and  to 
emphasize  those  factors  which  we  believe 
predispose  to  malignant  tumor  formation. 

In  the  production  of  a  malignant  neoplasm 
there  is  a  combination  of  factors  of  two  kinds, 
the  predisposing  or  intrinsic  factors  and  the 
exciting  or  extrinsic  factors.  Concerning  the 
nature  of  these  intrinsic  causes  we  have  at 
most  only  hypotheses  to  offer.  No  individual 
theory,  not  even  a  combination  of  them  all, 
ofifers  an  adequate  explanation;  but  inasmuch 
as  each  contains  some  truth  of  value  to  the 
clinicians,  they  merit  serious  consideration. 

Intrinsic  Causes 

Cohnheim's  Theory 

According  to  Cohnheim,  the  malignant 
neoplasm  has  its  inception  in  groups  of  cells 
that  have  become  arrested  in  the  development 
of  the  foetus.  These  cells  maintain  an  em- 
bryonic character  and  do  not  enter  into  the 


ETIOLOGY  1 1 

composition  or  the  functions  of  adult  tissues. 
They  are  therefore  called  embryonic  ''rests." 
Malformations  in  the  development  of  the  hu- 
man body  are  of  frequent  occurrence,  e.  g.y 
moles,  clefts,  naevi,  etc.;  and  it  has  been  the 
experience  of  every  observer  that  these  de- 
fects are  more  frequently  the  sites  of  malig- 
nancy in  later  years  than  the  normal  adult 
tissues. 

It  seems  logical  to  assume,  therefore,  as 
Cohnheim  does,  that  there  may  exist  congen- 
ital, microscopical  defects  in  the  formation 
of  tissues,  /.  ^.,  certain  groups  of  cells  become 
arrested  and  isolated  in  development,  form- 
ing "rests."  Every  mature  cell  has  a  twofold 
purpose,  (a)  growth,  (b)  the  performance 
of  some  specific  form  of  work,  e.  ^.,  secre- 
tion, contraction,  etc.  Since  the  cell  rests  do 
not  mature,  they  have  but  one  form  of  activ- 
ity— growth.  These  cells  may  remain  quies- 
cent in  the  tissues  of  which  they  were  in- 
tended to  become  a  part,  or  they  may  be 
transported  to  other  portions  of  the  body. 
Throughout  this  period  of  quiescence  the 
cells  maintain  their  vitality  undiminished,  but 
upon  the  intervention  of  an  exciting  cause, 
e.  g.,  irritation,  inflammation,  etc.,  they  are 
incited  to  an  unrestricted  proliferation  pro- 


12  CANCER 

ducing  a  malignant  tumor.  It  is  difficult  to 
understand  why  the  tumor  lies  latent  for  so 
many  years.  The  most  probable  explanation 
is  the  following:  During  health  the  activity 
of  the  neighboring  cells  of  the  tissue  or  organ 
hold  the  embryonic  "rests"  in  abeyance;  but 
when  the  functions  of  the  tissue  or  organ  be- 
come hampered  by  injury,  inflammation  or 
senility,  the  normal  cells  enter  upon  a  retro- 
gressive process,  and  the  dormant  "rests,"  no 
longer  constrained,  but  still  possessing  their 
embryonic  vigor,  begin  a  process  of  growth, 
paralleled  only  by  that  of  the  embryo. 

Every  clinician  will  find  many  of  his  ob- 
servations in  accordance  with  this  theory.  It 
is  most  frequently  after  the  menopause  that 
carcinomata  develop  in  the  uterus  and  breasts, 
and  in  a  large  majority  of  cases  of  malignancy 
of  the  stomach  a  previous  history  of  gastric 
ulcer  of  alcoholism  can  be  obtained. 

There  are,  on  the  other  hand,  many  weak 
points  in  Cohnheim's  hypothesis.  It  neces- 
sarily must  assume  a  widespread  distribution 
of  cell  "rests"  if  a  group  of  cells  is  to  be 
present  wherever  a  form  of  irritation  may 
be  encountered.  Moreover,  this  theory  alone 
fails  to  account  for  the  essential  characteris- 
tics   of    a    malignant  neoplasm — its  atypical 


ETIOLOGY  13 

growth  and  the  formation  of  metastases.  Al- 
though many  tumors  are  fcEtal  in  character 
in  the  human  body,  the  existence  of  dormant 
embryonic  cells  has  never  been  demonstrated. 


Ribbert's  Theory 

In  common  with  Cohnheim's  hypothesis, 
Ribbert  ascribes  the  origin  of  a  malignant 
tumor  primarily  to  an  isolated  group  of  cells. 
However,  according  to  the  latter  authority, 
the  process  of  isolation  is  attributed  not  to 
any  defect  in  the  development  of  the  cells 
themselves,  but  rather  to  an  atypical  develop- 
ment of  the  subjacent  connective  tissue.  The 
initial  stimulus,  then,  to  tumor  formation  is 
an  hyperplasia  of  the  connective  tissue,  in- 
duced by  trauma,  irritation  or  chronic  inflam- 
mation, which  severs  the  original  physiolog- 
ical connection  of  a  group  of  epithelial  cells 
from  their  neighbors  in  the  same  tissue  or 
organ.  Thus  isolated,  these  cells  are  no  longer 
subservient  to  the  common  cause  of  the  tissue 
or  organ,  but  they  are  still  imbued  with  an 
embryonic  capacity  for  growth,  and  if  the 
check  upon  growth  is  removed  by  diminished 
resistance,  they  proliferate  at  will,  thus  pro- 
ducing a  malignant  neoplasm. 


14  CANCER 

Of  interest  to  the  practitioner  are  these 
points  in  Ribbert's  hypothesis: 

(a)  The  process  of  "rest"  isolation  may  be 
post  natal  as  well  as  foetal,  e.  g.,  in  the  heal- 
ing of  a  wound  or  in  the  disturbance  of 
physiological  connection  of  a  portion  of  a 
tissue  or  organ  in  a  surgical  procedure. 

(b)  There  exists  a  precancerous  stage: 
e,  g.j  a  chronic  dermatitis  may  be  a  precan- 
cerous stage  in  the  formation  of  an  epitheli- 
oma. Or  in  the  development  of  carcinoma  of 
the  tongue  there  will  be  a  pre-existing  sub- 
epithelial reaction. 

(c)  Tumors  are  unicentric.  They  pro- 
gress by  the  division  of  their  own  cells,  and 
there  is  no  transitional  zone  between  the  tu- 
mor itself  and  the  normal  tissue.  It  may 
invade  and  thrust  apart  the  surrounding  cells, 
but  it  does  not  convert  them  into  tumor  cells. 

Ribbert's  theory,  however,  does  not  coin- 
cide with  facts  of  common  knowledge.  Ac- 
cording to  this  hypothesis  a  condition  most 
favorable  to  the  production  of  a  tumor  would 
be  the  healing  of  a  wound;  but  a  malignancy 
in  this  condition  is  very  rare.  Moreover,  in 
skin  grafts  a  proliferation  of  tissue  has  never 
been  recorded. 


ETIOLOGY  15 

The  Parasitic  Theory 

In  a  certain  biological  sense  every  neo- 
plasm is  a  parasite,  for  it  lives  and  grows  at 
the  expense  of  another  organism — its  host.  It 
is  not,  however,  with  this  significance  that  we 
speak  of  the  parasitic  nature  of  cancer.  The 
earliest  observers  ascribed  the  origin  and  the 
propagation  of  the  disease  to  microorganisms, 
and  even  at  the  present  day  a  few  authorities 
adhere  to  that  view  of  cancer  formation. 

The  theory  of  the  parasitic  origin  of  ma- 
lignant tumors  is  not  without  some  founda- 
tion. Although  it  is  not  uncommon  to  find 
bacteria  in  and  around  malignant  growths, 
there  is  no  evidence  to  connect  their  activity 
with  tumor  formation.  We  must  always  bear 
in  mind  the  fact  that  the  ulceration  is  not  the 
cancer^  but  that  in  the  vicinity  of  a  malig- 
nant neoplasm  the  natural  protective  powers 
of  the  tissue  cells  are  inhibited,  and  therefore 
the  site  of  a  malignancy  becomes  a  fertile  field 
for  bacterial  growth. 

One  of  the  authors  has  had  the  opportu- 
nity of  following  several  cases  of  cancer  that 
received  B.  Prodigiosus  vaccine.  One  of 
these  cases,  in  which  the  site  of  operation  did 
not  heal  following  the  removal  of  a  tumor 


1 6  CANCER 

from  the  abdomen,  manifested  no  improve- 
ment. In  the  other  cases  of  epithelioma  with 
superimposed  suppurative  processes,  an  ap- 
parent improvement  in  checking  the  progress 
of  the  infection  was  observed.  This  improve- 
ment must  be  attributed  to  a  stimulation  of 
antibody  formation  in  the  blood  of  the  host 
which  enabled  the  host  to  ward  ofif  the  infec- 
tion, but  not  the  neoplasm.  All  the  cases, 
however,  terminated  fatally. 

Minute  bodies,  of  an  intracellular  or  an 
extracellular  type,  with  staining  properties 
essentially  different  from  the  tumor  cells, 
have  been  demonstrated  about  cancerous 
growths.  Some  authorities,  as  Russel  and 
Romcalli,  have  considered  them  blastomy- 
cetes,  while  others  look  upon  them  as  intra- 
cellular protozoa.  It  has  been  found,  how- 
ever, that  their  occurrence  is  not  confined  to 
malignant  neoplasms,  but  they  also  frequently 
accompany  inflammatory  conditions.  It  is 
generally  agreed  now  that  these  bodies  are 
products  of  the  cell  metabolism  suspended  in 
the  cytoplasm  or  extruded  into  the  intracellu- 
lar spaces. 

The  all-important  and  much  mooted  ques- 
tion of  the  infectivity  of  carcinoma  and  sar- 
coma depends  upon  the  substantiation  of  their 


ETIOLOGY  17 

parasitic  origin.  That  there  is  a  strong  popu- 
lar conviction  of  the  possible  transference  of 
the  disease  from  one  person  to  another  is  evi- 
dent to  everyone  experienced  in  history-taking 
among  patients  of  this  type.  The  onset  of  the 
malady  will  be  dated  from  and  attributed  to 
actual  contact  with  an  affected  person,  as  in 
the  dressing  of  a  cancerous  patient,  or  the 
use  of  the  same  dishes  or  drinking  cups.  If 
carefully  examined,  it  will  be  found  that  with 
the  exception  of  a  few  striking  coincidences, 
the  greater  part  of  these  histories  will  not 
bear  scrutiny.  On  the  contrary,  we  possess 
the  more  reliable  evidence  that  there  is  no 
instance  on  record  of  an  infection  among 
nurses,  clinicians  or  pathologists,  nor  do  they 
possess  an  undue  liability  or  immunity  toward 
cancer.  The  only  evidence  conclusive  of 
the  existence  of  a  parasitic  micro-organism  as 
the  causative  agent  in  the  production  of  can- 
cer would  be  the  actual  demonstration  of  the 
microbe  invariably  present  in  tumors  and 
capable  of  producing  histologically  identical 
growths  when  transmitted  to  other  hosts.  The 
lack  of  such  evidence,  however,  leaves  the 
question  an  open  one.  It  is  indeed  true  that 
all  types  of  micro-organisms,  cocci,  bacilli, 
blastomycetes,  protozoa  and  metazoa,  have  at 


1 8  CANCER 

one  time  or  another  been  associated  with  the 
etiology  of  cancer,  and  in  fact  the  variety  of 
these  alleged  causative  agents,  far  from  con- 
vincing, has  rather  increased  our  scepticism. 
For  a  time  the  Micrococcus  neoformans^  de- 
scribed by  Doyen,  received  more  serious  con- 
sideration than  the  others.  The  Micrococcus 
neoformans  is  closely  allied  to  the  Staphylo- 
coccus albusj  and,  according  to  Doyen,  is  in- 
variably found  in  the  vicinity  of  new  growths, 
and  animals  experimentally  inoculated  with 
the  coccus  develop  malignant  neoplasms. 
Later  workers,  however,  have  not  only  failed 
to  isolate  the  organism  from  malignant  tu- 
mors, but  they  have  shown  that  many  tumors 
are  sterile. 

There  can  be  no  question  but  that  certain 
parasites,  such  as  metazoa,  play  an  important 
role  in  cancer  formation,  but  their  causation 
is  rather  secondary  than  primary,  /.  ^.,  one  of 
irritation.  We  can  conceive  of  a  chronic  irri- 
tation due  to  a  parasitic  infection,  stimulat- 
ing a  latent  malignancy  in  an  organism  where 
the  primary  cause,  /.  ^.,  predisposition,  was 
previously  active.  But  the  influence  of  the 
parasite  in  such  a  case  is  in  no  way  analogous 
to  the  part  taken  by  the  tubercle  bacillus  in 
the  production  of  tuberculosis. 


ETIOLOGY  19 

The  results  obtained  in  the  experimental 
production  of  cancerous  growths  have  demon- 
strated beyond  a  possibility  of  doubt  that  for 
the  successful  transference  of  a  neoplasm  from 
one  host  to  another  the  intact  cancer  cell  is 
essential.  Attempts  to  inoculate  animals  with 
products  of  the  cancer  cells,  or  with  para- 
sites isolated  from  the  growth,  have  invari- 
ably failed.  If,  therefore,  a  specific  organism 
does  exist,  it  must  be  essentially  different 
from  all  micro-organisms  within  the  scope 
of  our  present  knowledge.  In  view  of  the 
evidence  afforded  by  clinical  observations  and 
experimental  study,  we  must  not  regard  can- 
cer as  a  parasitic  disease  in  the  accepted  sig- 
nificance of  that  term.  There  is  then  no 
possibility  of  infection  save  by  inoculation 
with  the  living  cancer  cell.  Further,  although 
the  ulceration  is  not  the  cancer  or  the  cause 
of  it,  there  is  every  need  of  keeping  the 
growth  aseptic  by  agents  described  in  a  later 
chapter,  if  we  are  to  preserve  the  vitality  of 
the  neighboring  tissue  cells  and  to  assist  their 
protective  forces. 

The  theories  so  far  discussed  are  not  indi- 
vidually sufficient  to  account  either  for  the 
formation,  propagation,  or  the  transmission 
of   malignant   growths.      All   of    them   have 


20  CANCER 

many  good  points;  so,  too,  all  of  them  have 
their  weak  points.  It  will  be  noted  that  they 
bring  into  consideration  the  pathology  of  ma- 
lignant tumors.  In  fact  this  might  be  ex- 
pected when  we  recall  that  their  authors  were 
pathologists  of  the  old  school,  who  considered 
nothing  worthy  of  consideration  unless  it 
could  be  shown  under  the  microscope.  How- 
ever, with  the  recent  advance  in  the  chemistry 
of  living  organisms,  many  facts  have  been 
brought  to  light  that  have  revolutionized  our 
conception  of  the  factors  influencing  the  de- 
velopment of  pathological  conditions.  Re- 
cent investigations  in  the  composition  of  the 
blood  and  the  other  body  fluids,  in  patients 
suffering  from  carcinoma  and  sarcoma,  have 
demonstrated  that  these  fluids  differ  widely 
from  the  composition  of  normal  fluids.  It  will 
be  observed,  as  stated  in  a  later  chapter,  that 
the  blood  of  patients  suffering  from  malig- 
nancies shows  an  increase  in  non-protein  nitro- 
gen, as  well  as  an  increase  in  non-protein  sul- 
phur. Our  own  investigations  have  shown  that 
this  increase  in  the  non-protein  and  non-oxi- 
dized sulphur,  continually  known  as  neutral 
sulphur,  shows  also  in  the  urine.  It  is  also  men- 
tioned by  Greenwald,  "Increase  in  sulphur  in 
Urine,"  Journal  of  Cancer  Research^  ^9^7- 


ETIOLOGY  21 

There  are  two  possible  exceptions  to  the 
occurrence  of  the  abnormal  amount  of  nitro- 
gen and  sulphur  in  the  blood.  They  may  be 
due  to  the  presence  of  a  combination  which 
we  call  toxemia,  being  both  nitrogen  and 
sulphur,  but  differ  from  the  ordinary  com- 
pounds with  which  we  are  familiar  in  the 
blood,  as  urea  and  so  on.  The  presence  of 
this  toxemia  may  incite  epithelial  cells  or  con- 
nective tissue  cells  to  an  unrestricted  prolif- 
eration. It  may  be  that  these  cells  are  iso- 
lated from  their  neighbors,  as  rests,  as  Cohn- 
heim  thinks,  but  the  exciting  cause  would  be 
the  presence  of  this  compound  or  compounds 
detected  by  the  increase  of  nitrogen  and  sul- 
phur in  the  blood  stream.  It  is  interesting  to 
note  in  this  communication  that  Jacques  Loeb 
has  recently  shown  that  unfertilized  ova  may 
be  incited  to  greater  and  more  mature  devel- 
opment by  the  agency  of  certain  chemical 
substitutes.  In  an  analogous  manner  the 
presence  of  this  compound  or  compounds  in 
the  blood  stream  may  incite  cells  to  unre- 
stricted proliferation.  On  the  other  hand, 
the  compound  containing  this  nitrogen  and 
sulphur  may  be  a  product  of  the  metabolism 
of  the  carcinoma  or  the  sarcoma,  which  finds 
its  way  into  the  blood  stream.     If  this  latter 


22  CANCER 

view  be  true,  then  the  metabolism  of  the  ma- 
lignant cells  varies  from  the  metabolism  of 
healthy  cells,  because  in  the  latter  case  we  find 
as  metabolic  products,  urea,  creatinine,  and 
uric  acid.  The  compound  indication  of  the 
presence  of  the  malignancy  is  none  of  these 
three.  No  matter  what  our  conception  of 
the  nature  of  a  cancer  may  be,  the  fact  re- 
mains that  its  presence  in  the  organism  is 
attended  by  an  increase  of  the  non-protein 
nitrogen  and  sulphur,  and  this  fact  is  most 
valuable  in  diagnosing  a  latent  malignant 
tumor  or  in  differentiating  a  malignant  from 
a  benign  tumor. 


CHAPTER    II 
Heredity 

The  subject  of  heredity  in  connection  with 
malignant  growth  is  such  an  important  one, 
and  one  which  at  the  present  time  is  attract- 
ing so  much  attention,  that  we  feel  obliged  to 
mention  it,  although  our  views  concerning  it 
are  not  so  well  fortified  but  that  they  are  sub- 
ject to  modification  in  the  future  as  a  result 
of  the  publication  of  investigations  that  are 
being  carried  on  at  the  present  time  by  work- 
ers in  this  field. 

If  the  human  organism  reacted  to  disease 
in  exactly  the  way  that  certain  animals  do, 
such  as  mice,  we  would  be  justified  in  hold- 
ing the  same  conceptions  concerning  the  na- 
ture of  this  disease  as  are  held  by  Miss  Maud 
Slye,  of  the  Ortho  Sprague  Institute,  Chi- 
cago, the  results  of  whose  researches  have  been 
published  from  time  to  time  in  the  Journal 
for  Cancer  Research  during  the  years  of 
1916  and  1917.  Her  results  seem  to  show 
that  mouse  cancer  is  transmissible  exactly  ac- 

23 


24  CANCER 

cording  to  the  laws  of  the  so-called  ^'Men- 
delian  Theory."  This  theory  was  first  pro- 
mulgated through  work  on  peas  by  Gregor 
Johann  Mendel  in  1866,  and  within  the  last 
ten  years  has  attracted  much  attention.  The 
most  exhaustive  of  many  works  on  the  sub- 
ject, and  one  to  which  we  would  call  atten- 
tion, is  that  by  Bateson,  published  in  1913. 
The  theory  can  be  perhaps  more  easily  illus- 
trated by  giving  the  results  of  some  investi- 
gations on  Andalusian  pigeons,  results  which 
correspond  with  the  work  done  by  Mendel 
on  peas.  If  fifty  white  and  fifty  black  Anda- 
lusian pigeons  are  mated,  the  result  would 
be  one  hundred  blue  pigeons.  If  these  blue 
pigeons,  which  are  the  second  generation,  are 
mated  among  themselves,  the  result  in  the 
third  generation  will  be  twenty-five  white, 
twenty-five  black,  and  fifty  blue  pigeons.  The 
twenty-five  white  would  breed  true  to  white, 
the  twenty-five  black  would  breed  true  to 
black,  and  the  fifty  blue  would  continue  to 
breed  the  following  generation  in  the  same 
proportion,  one-half  blue,  one-quarter  white, 
and  one-quarter  black. 

Quoting  from  the  Catholic  Encyclopedia 
under  ''Mendel,"  the  results  of  his  work  on 
peas  were  as  follows:  "In  the  case  of  the  pea, 


HEREDITY  25 

he  observed  that  some  were  tall,  some  dwarf 
in  habit;  some  had  round  seeds,  others  wrin- 
kled; some  had  green  endosperm,  others  yel- 
low. For  the  purpose  of  his  own  observation 
he  selected  seven  such  characters  and  studied 
their  behavior  under  hybridization.  From 
what  occurred  he  was  led  to  believe  that  the 
progeny  of  the  various  crosses  behaved  in 
regard  to  these  characters  not  in  a  haphazard 
manner,  but  in  one  which  was  reducible  to 
the  terms  of  a  so-called  ^'Natural  Law."  One 
instance  given  by  Bateson  will  explain  what 
happens:  there  are  tall  and  short  (or 
''Cupid")  sweet  peas,  and  in  them  we  have 
plants  showing  a  pair  of  marked  and  easily 
recognizable  opposite  characters.  The  tall 
and  short  forms  are  crossed  with  one  another, 
and  the  seeds  are  collected  and  sown.  The 
resultant  plants  will  be  found  to  belong  en- 
tirely to  the  tall  variety,  which  has  apparently 
wiped  out  the  short.  If,  however,  this  gen- 
eration of  seeds  is  sown  and  the  flowers  of 
the  resultant  plants  be  self-fertilized,  the  re- 
sult is  that,  when  their  seeds  are  sown  and 
have  sprung  up  into  plants,  it  is  found  that 
these  are  mixed,  and  mixed  in  definite  pro- 
portions, for  on  the  average  it  will  be  found 
that  there  are  three  tall  forms  for  every  one 


26  CANCER 

of  the  short.  It  follows  that  the  dwarfishness 
was  not  wiped  out,  but  that  it  was  tempora- 
rily obscured  in  the  second  generation,  though 
present  all  the  time  potentially.  To  the  char- 
acter which  alone  appears  in  the  first  cross  is 
given  the  name  dominant  (in  this  instance 
tallness  is  dominant)  and  to  the  hidden  char- 
acter that  of  recessive  (dwarfishness  in  the 
example).  When  the  tails  and  dwarfs  of  the 
third  generation  are  allowed  to  be  self-fer- 
tilized, it  is  found  that  all  the  recessives 
(dwarfs)  breed  true,  and  what  is  more,  will 
go  on  breeding  true  as  long  as  uninterfered 
with.  Not  so  with  the  dominants  which, 
after  self-fertilization,  produce  both  tails  and 
dwarfs.  Some  of  the  tails  of  this  generation 
will  breed  true  and  continue  to  breed  true; 
others  will  not,  but  produce  a  mixed  progeny. 
Hence,  out  of  the  first  plants,  seventy-five  will 
be  tails  (dominants)  and  twenty- five  dwarfs 
(recessives),  these  last  being  pure.  Of  the 
seventy-five  tails,  twenty-five  will  be  pure 
and  w^U  go  on  producing  tails;  fifty  will  be 
mixed,  and  their  progeny  will  consist  of  pure 
dominants,  mixed  dominants,  and  recessives, 
as  has  been  stated  above." 

As  we  have  understood  the  work  done  by 
the  investigator  in  mouse  cancer,  previously 


HEREDITY  27 

referred  to,  transmission  of  cancer  in  mice 
follows  out  Mendel's  laws  along  the  lines 
above  mentioned.  And  not  only  does  it  seem 
true  about  mouse  cancer  in  general,  but  cer- 
tain types  of  cancer  in  them,  like  cancer  of 
the  liver  (by  proper  mating  of  the  mice), 
seem  to  develop  according  to  Mendel's 
laws. 

We  are  inclined  to  believe  that,  as  regards 
human  beings,  statistics  so  far  are  unable  to 
demonstrate  any  such  conditions  as  those  in 
the  mice  above  referred  to,  but  it  is  one  of 
those  matters  that  time  and  proper  study 
of  cases  and  their  classification  will  finally 
clear  up. 

Somewhat  generally  speaking,  there  seems 
to  be  no  doubt  that  a  tendency  to  cancer  ex-  1 
ists  in  some  families;  and  if  this  be  true,  as 
we  believe  it  to  be,  we  may  also  recall  the 
physiological  suggestion  referred  to  in  other 
chapters,  that  a  toxin  may  pass  from  the  pla- ) 
centa  to  the  foetal  circulation,  predisposing 
the  foetus  to  a  malignant  formation  at  the  in- 
tervention of  the  secondary  cause.  It  appears, 
to  us  that,  if  cancer  is  inherited,  the  geo- 
graphical history  of  cancer  should  have  some 
bearing  on  the  subject,  and  to  some  extent  we 
have  carried  on  investigations  of  our  own  in- 


28  CANCER 

this  direction,  although  not  enough  to  have 
derived  from  them  alone  positive  conclusions. 
Investigations  as  to  the  character  of  disease 
on  an  island  (Pitcairns  Island),  which  is  so 
remote  from  civilization  that  mixture  of  for- 
eign blood  has  practically  never  been  intro- 
duced, shows  that  cancer  has  never  been  seen. 
This  is  on  the  authority  of  Miss  McCoy,  a 
trained  nurse,  a  resident  of  the  island,  who 
recently  visited  this  country. 

On  some  other  small  islands,  not  far  from 
each  other,  in  the  West  Indies,  but  not  so 
much  isolated,  there  is  a  large  mortality  from 
malignant  growth,  while  in  the  neighboring 
island  it  is  very  small. 

The  above  data,  while  not  conclusive,  and 
not  definite  enough  to  be  of  much  scientific 
value,  strengthen  our  views  as  to  the  part 
played  by  heredity  in  cancer.  This,  combined 
with  what  we  have  been  able  to  find  out  about 
the  animal  transmission  as  mentioned  above, 
with  the  knowledge  we  have  of  the  transmis- 
sion of  other  diseases  resembling  cancer, 
backed  up  with  our  clinical  experience — 
while  the  exact  method,  the  exact  proportion, 
or  the  exact  laws  governing  such  transmissions 
in  human  beings  is  still  a  subject  to  be  defi- 
nitely settled  in  the  future — have  given  us  a 


HEREDITY 


29 


very  positive  belief  that  there  exists  a  hered- 
itary tendency  to  cancer  transmission;  but 
with  the  exact  physiological  and  anatomical 
laws  governing  these  we  are  not  as  yet  fa- 
miliar. 


PART  II 
NATURE  OF  CANCER 

CHAPTER  I 

Nature  of  Cancer 

We  wish  to  make  it  clear  that,  in  this  chap- 
ter as  well  as  the  preceding  ones,  we  have  no 
desire  to  overload  this  little  volume  with  ma- 
terial which  can  easily  be  obtained  by  those 
particularly  interested  in  the  subject,  more 
fully  from  many  of  the  more  recent  works, 
written  by  men  more  familiar  than  ourselves 
with  the  pathological  and  histological  tech- 
nique; but  it  has  seemed  wise  to  call  atten- 
tion to  the  conclusions  most  generally  accepted 
at  the  present  time,  hoping  that  by  such  means 
this  book  may  be  more  of  an  aid  to  those  in- 
terested in  the  diagnosis  of  cancer  who  may 
not  have  the  opportunity  to  obtain  this  infor- 
mation or  are  not  already  conversant  with  it. 
At  the  same  time  it  helps  to  make  clear  any 
theories  of  our  own  we  have  desired  to  pub- 
lish and  enables  us  to  present  the  results  of 

30 


NATURE  31 

any  original  work  which  we  have  done  in  a 
somewhat  more  suitable  setting. 

Cancerous  growths  partake  of  the  nature 
of  tumors,  and  hence  a  discussion  of  the 
characteristics  of  tumors  from  a  pathological 
standpoint  will  be  essential  before  we  can 
consider  the  minute  structure  of  cancerous 
growths.  Powell  White  has  defined  a  tumor 
as  a  mass  of  cells,  tissues,  or  organs,  resem- 
bling those  normally  present  in  the  body,  but 
arranged  atypically,  which  grow  at  the  ex- 
pense of  the  organism,  without  at  the  same 
time  subserving  any  useful  purpose  in  the 
host.  This  definition  most  satisfactorily  ful- 
fills all  the  conditions  noted  by  pathologists 
or  surgeons  in  connection  with  tumors  in  gen- 
eral. All  tumors  are  derived  from  pre- 
existent  cells  of  the  body,  which  they  re- 
semble more  or  less  closely.  However,  in 
certain  conditions  the  characteristics  of  the 
cells  may  revert  to  a  primitive  form  so  that 
they  no  longer  resemble  the  cells  of  the  tis- 
sues from  which  they  were  derived.  Hence 
their  origin  is  defined.  Tumors  whose  cells 
preserve  the  characteristics  of  the  original 
tissue  or  organ  are  called  typical  growths, 
but  where  the  original  characteristics  of  the 
parent  tissue  or  organ  are  lost  the  growth  is 


32  CANCER 

spoken  of  as  atypical.  All  tumors  are  com- 
posed of  two  structures,  a  matrix  or  stroma, 
and  the  parenchyma  or  the  tumor  cell  proper. 
It  is  the  nature  of  the  parenchyma  that  gives 
the  tumor  its  distinctive  features.  In  various 
tumors  a  wide  variation  in  the  relation  of  the 
parenchyma  to  the  stroma  will  be  noted.  The 
general  statement  may  be  made  that  benign 
tumors  are  typical.  In  malignant  tumors,  on 
the  other  hand,  the  cells  differ  considerably 
from  the  parent  cells.  There  is  noted  a  re- 
version to  the  embryonic  or  vegetative  form 
of  cell,  and  this  reversion  is  spoken  of  as  ana- 
plasia.  There  exists  a  close  relationship  be- 
tween the  histological  structure  of  the  cell 
and  its  pathology.  That  is  to  say,  in  innocent 
tumors  the  cells  which  still  preserve  the 
morphology  of  the  parent  may  continue  to 
perform  the  functions  of  the  organ  or  tissue 
from  which  they  were  derived;  but,  on  the 
contrary,  in  malignant  tumors  where  a  varia- 
tion from  the  prototype  occurs,  all  functions 
are  lost  except  that  of  growth.  In  the  nucleus 
of  the  parenchymatous  cells  some  new  changes 
will  be  observed  in  typical  growths.  The 
nuclei  are  normal,  but  in  atypical  growths 
wide  variations  occur  in  the  size  or  shape  of 
the  nucleus,  or  in  multiplication,  or  in  de- 


NATURE  33 

generative  changes.  The  most  common  form 
of  variation  occurs  in  the  character  of  cell 
division;  that  is,  in  rapidly  growing  tumors 
instead  of  indirect  cell  division  or  mitosis 
we  shall  note  particularly  around  the  margin 
of  the  growth  evidences  of  direct  cell  division 
or  karyokinesis. 

The  supporting  network  of  the  tumor  or 
its  matrix  is  an  outgrowth  of  the  stroma  from 
the  parent  tissue.  It  carries  the  vascular  and 
lymph  supply  to  the  tumor.  In  the  benign 
type  the  blood  vessels  are  well  developed,  but 
in  the  malignant  type  they  are  capillaries,  and 
very  often  consist  merely  of  a  lining  of  endo- 
thelial cells.  The  lymph  supply  is  principally 
through  lymph  spaces.  No  nerves  have  been 
found  in  tumor  stroma.  Occasionally  around 
the  periphery  one  may  find  nerve  tissue  that 
has  become  incorporated  in  the  tumor  by  the 
invasion  of  neighboring  tissue.  A  sponta- 
neous disappearance  of  a  tumor  or  a  check 
in  its  growth  may  occur,  owing  to  a  prolif- 
eration of  the  connective  tissue  which  chokes 
the  neoplastic  elements.  However,  under 
other  conditions  the  stroma  may  assume  ma- 
lignant characteristics  and  proliferate  in  pro- 
portion to  the  parenchyma.  Or,  on  the  other 
hand,  it  may  undergo  calcareous  degenera- 


34  CANCER 

tion.  In  innocent  tumors  no  variation  in  the 
character  of  the  connective  tissue  will  be 
found  and  the  parenchyma  and  stroma  occur 
side  by  side. 

The  method  by  which  tumors  proliferate 
has  been  a  subject  of  dispute  among  patholo- 
gists. Some  authorities  have  claimed  that 
the  tumor  cells  cause  a  degeneration  in  the 
cells  of  neighboring  tissue,  and  that  this  de- 
generation is  a  reversion  to  the  type  of  cell 
in  the  parenchyma  of  the  tumor.  These  de- 
generative, changes  have  been  reported  prin- 
cipally around  the  periphery  of  the  tumor,  but 
it  has  been  impossible  to  substantiate  such  a 
claim,  because  what  may  appear  to  be  a  sin- 
gle tumor,  on  careful  examination  will  ap- 
pear to  be  a  multiple  tumor.  However,  the 
more  logical  view  entertained  by  the  majority 
of  pathologists  is  that  tumors  are  unicentric, 
that  is,  they  propagate  by  expansion  and  in- 
filtration. When  a  tumor  occurs  by  expan- 
sion the  increase  in  the  tumor  substance  is 
uniform  throughout.  This  type  of  growth  is 
the  rule  in  typical  tumors.  Malignant  tumors 
prefer  to  grow  by  infiltration,  that  is,  by 
peripheral  extension,  with  little  or  no  growth 
in  the  center  of  the  tumor,  in  fact  the  central 
portion,  deprived  of  its  blood  supply,  may 


NATURE  35 

undergo  a  degenerative  change  or  a  necro- 
biosis. From  the  point  of  view  ot  the  sur- 
geon and  the  clinician  the  most  pertinent 
classification  of  tumors  is  into  groups,  the 
innocent  and  the  malignant.  The  clinician's 
conception  of  malignancy  is  radically  differ- 
ent from  that  of  the  pathologist.  To  the  clini- 
cian the  growth  which  eventually  entails  a 
fatal  termination  of  the  host  is  considered 
malignant.  The  pathologist,  on  the  con- 
trary, classifies  as  malignant  those  tumors 
whose  cells  possess  definite  characteristics, 
and  the  tumor  as  a  whole  manifests  properties 
which  experience  has  shown  to  necessitate  a 
fatal  prognosis  to  the  host.  In  other  words, 
to  the  clinician  the  criterion  of  malignancy  is 
the  prognosis,  but  to  the  pathologist  it  is  the 
properties  of  the  gross  structure  and  its  his- 
tological characteristics.  Those  properties 
which  have  been  found  by  experience  to  be 
invariably  associated  with  pathologically  ma- 
lignant tumors  are,  first,  rapidity  of  growth; 
second,  the  vegetative  or  embryonic  nature  of 
the  cells;  third,  infiltration;  fourth,  the  for- 
mation of  metastases  leading  to  a  local  recur- 
rence; fifth,  ulceration;  sixth,  a  tendency  to 
degenerative  changes;  and,  seventh,  the  pro- 
duction of  cachexia  and  subsequent  anemia. 


36  CANCER 

The  rate  of  growth  is  not  an  invariable  in- 
dication of  the  nature  of  the  tumor.  The 
general  statement  that  malignant  neoplasms 
manifest  a  rapidity  of  growth,  while  benign 
tumors  are  slow  growing,  admits  of  many  ex- 
ceptions. A  slow-growing  tumor  is  not  nec- 
essarily innocent.  Sarcomata,  however,  are 
almost  invariably  rapid  in  growth.  Micro- 
scopically, this  rapidity  of  growth  is  indicated 
by  a  peripheral  invasion  of  adjacent  struc- 
tures and  in  the  peripheral  cells  there  will  be 
noted  numerous  points  of  mitosis.  The 
growth  of  the  malignant  tumor  is  independent 
of  the  physical  condition  of  the  host. 

Character  of  the  Cell. — It  was  noted  above 
that  cells  of  malignant  neoplasms  manifest  a 
tendency  to  a  reversion  to  the  primitive  type, 
and  this  reversion  has  been  called  by  Hause- 
mann  "anaplasia."  For  mature  cells,  posses- 
sion of  two  functions  is  necessary:  (i)  of 
growth,  and  (2)  the  performance  of  some 
specific  work,  e.  g.^  secretion,  contraction,  and 
so  on.  When  such  a  cell  undergoes  a  process 
of  anaplasia  its  specific  function  is  lost,  and 
all  the  energy  within  the  cell  is  expended  in 
unrestrained  growth.  Microscopical  exami- 
nation of  cells  will  show  evidence  of  the  per- 
formance of  their  specific  work,  as,  for  in- 


NATURE  37 

Stance,  the  cells  of  mucous  membranes  will 
be  observed  to  contain  mucin,  and  this  mucin 
occurs  in  the  cytoplasm,  and  frequently  gives 
the  cell  a  goblet  appearance.  When  anaplasia 
takes  place,  the  cytoplasm  vs^ill  be  seen  to  have 
diminished.  The  goblet  appearance  of  the 
cells  is  no  longer  noted  and  the  nuclei  are 
relatively  larger  than  under  normal  condi- 
tions. It  must  be  borne  in  mind,  however, 
that  a  diagnosis  cannot  be  made  upon  changes 
in  one  cancer  cell,  but  an  examination  of  the 
tumor  as  a  whole  must  be  made,  and  if  ana- 
plasia is  noted  to  be  the  rule  throughout  the 
tumor,  then  it  may  safely  be  classified  as  ma- 
lignant. 

Metastasis. — The  characteristic  of  neo- 
plasms of  the  malignant  type,  which  renders 
their  removal  by  surgical  means  a  practical 
impossibility,  is  the  ability  to  form  secondary 
growths  of  a  similar  character  at  a  distance 
from  the  original  tumor,  and  this  character- 
istic is  called  metastasis.  But  metastasis  must 
be  distinguished  carefully  from  a  local  re- 
currence. The  latter  is  the  reappearance  of 
the  malignant  process  in  the  immediate  neigh- 
borhood of  the  original  neoplasm.  The  for- 
mation of  metastasis  has  been  shown  to  be  due 
to  the  spreading  of  intact  cancer  cells  from 


38  CANCER 

the  primary  focus  to  a  distant  site  by  a 
combination  of  three  processes:  first,  by  the 
lymphatic  system;  second,  by  the  venous  sys- 
tem; and  third,  by  the  arterial  system.  In  a 
dissemination  of  cancerous  cells  the  lymphatic 
system  plays  the  most  important  part.  Such, 
however,  is  not  true  of  sarcomata,  and  most 
probably  this  is  due  to  the  fact  that  the  char- 
acteristic cells  of  sarcoma,  which  are  larger 
than  those  of  carcinoma,  cannot  pass  through 
the  lymph  walls,  and  consequently  they  are 
passed  on  to  the  vascular  system.  The  car- 
cinomata  cells,  however,  filter  out  through 
the  lymph  walls  before  they  reach  the  vas- 
cular system.  Cells  from  primary  cancerous 
growths  may  escape  into  the  lymph  system, 
where  they  will  be  transported  until  they  be- 
come fixed,  and  at  such  point  of  fixation  they 
proliferate  and  produce  a  secondary  growth. 
Cancer  cells  from  the  primary  growth  may 
escape  into  the  lymphatic  system.  An  accu- 
mulation of  such  cells  and  their  fixation,  with 
consequent  proliferation  along  the  lymphat- 
ics, may  cause  the  formation  of  a  series  of 
nodules,  thus  producing  what  is  known  as 
lymphangitis  carcinomatosis.  On  the  other 
hand,  the  cells  may  not  become  fixed  until 
they  reach  the  first  lymph  glands.    The  pro- 


NATURE  39 

liferation  of  the  malignant  cells  here  will 
give  rise  to  growths  very  similar  to  the  orig- 
inal tumor.  In  the  draining  of  the  lymph 
through  the  lymph  glands  we  would  expect 
the  first  series  of  glands  to  be  involved,  /.  e., 
to  manifest  evidences  of  metastatic  growths. 
This  is  a  very  important  diagnostic  and  prog- 
nostic sign.  Almost  invariably,  in  cases  of 
malignant  neoplasms,  secondary  tumors  will 
be  found  in  the  lymph  glands  that  are  the 
first  to  receive  the  lymph  from  the  neighbor- 
hood of  the  original  tumor.  When,  however, 
the  invasion  has  extended  beyond  the  first  to 
the  second  series  of  glands,  then  the  case  must 
be  considered  inoperable.  Thus,  in  a  case  of 
malignancy  of  the  forearm,  the  first  glands 
to  show  metastatic  growths  will  be  the  glands 
of  the  antecubital  fossa.  However,  if  the 
glands  of  the  axilla  also  are  involved,  we 
must  consider  the  dissemination  of  metastases 
too  widespread  to  be  relieved  by  surgical  in- 
tervention. The  primary  function  of  a  lymph 
gland  is  to  check  the  spread  of  infection  by 
draining  infecting  agents  from  the  lymph 
stream,  thus  preventing  them  from  entering 
the  vascular  system.  The  lymphatics  can 
check  cancer  only  for  a  time,  and  when  the 
cells  have  passed  the  first  series  of  glands  and 


40  CANCER 

have  reached  the  second,  this  means  that  the 
first  barriers  have  been  passed  and  most  prob- 
ably the  invading  cells  have  entered  the  blood 
stream. 

An  invasion  of  the  venous  branch  of  the 
vascular  system  may  take  place  in  two  ways, 
by  the  passage  of  the  cancer  cells  from  the 
lymph  system  into  the  veins,  or  by  the  direct 
invasion  of  the  wall  of  the  vein.  In  the  first 
case  numerous  metastases  will  be  formed 
throughout  the  lymphatic  system  and  else- 
where. In  the  second  case,  when  the  malig- 
nant cells  have  found  their  way  into  the  in- 
tima  and  have  eroded  this,  an  extension  of 
the  growth  into  the  vein  follows.  If  the  vein 
involved  is  of  any  considerable  size,  a  fatal 
hemorrhage  is  the  issue.  Whether  the  vein 
be  invaded  in  one  way  or  the  other,  metastatic 
growth  will  develop  promptly  in  the  lungs. 
It  may  be  said  that  a  growth  manifesting 
hemorrhages  has  already  involved  the  blood 
vessels,  and  therefore  the  blood  stream  has 
been  burdened  with  intact  cells  that  will  pro- 
duce metastatic  growths. 

An  extension  of  cancer  cells  into  the  ar- 
terial system  is  less  common  than  the  inva- 
sion of  the  venous  system.  The  arterial  walls 
ofifer  greater  resistance  to  the  invasion  of  the 


NATURE  41 

growth.  Cancer  cells  that  primarily  entered 
the  lymphatic  system  are  removed  from  the 
blood  before  it  reaches  the  arteries.  Cancer 
cells  entering  the  arteries  would  be  carried 
to  the  periphery,  where  they  would  be 
blocked  by  the  capillaries,  producing  periph- 
eral metastatic  growths.  Veins,  however, 
carry  the  cells  centrally.  Secondary  growths 
even  from  primary  peripheral  tumors  are 
more  frequently  located  centrally  than  in  the 
extremities. 

In  the  peritoneal  and  thoracic  cavities, 
metastases  may  occur,  independent  of  the 
lymph  or  blood  supply.  Thus,  a  cancer  of 
the  stomach  may  produce  a  secondary  growth 
in  the  ovaries  or  rectum.  Such  secondary 
growths  are  due  to  the  fact  that  cells  become 
dislodged  from  the  original  growth  through 
the  movements  of  the  viscera,  or  by  surgical 
manipulation,  or  palpation.  Such  cells  may 
be  carried  to  a  distant  part  of  the  cavity  by 
the  peritoneal  or  pleural  fluid,  and  wherever 
they  become  fixed  produce  secondary  tumors. 

Our  advice  to  the  clinicians,  then,  is  to 
avoid  all  unnecessary  manipulation  of  tumors 
suspected  of  possessing  malignant  character- 
istics or  a  tendency  thereto. 

Recurrence. — From  the  point  of  view  of 


42  CANCER 

clinical  medicine  the  salient  feature  of  ma- 
lignant tumors  is  their  tendency  to  local  re- 
currence, that  is,  to  appear,  after  their  re- 
moval, in  the  vicinity  of  the  original  growth. 
The  fact  that  tumor  excisions  have  been 
ineffectual  in  promoting  permanent  cures 
must  be  attributed  to  this  property,  charac- 
teristic of  malignancies.  Obviously  it  is  of 
little  value  as  a  diagnostic  sign;  however,  a 
knowledge  of  the  means  by  which  recurrence 
takes  place  is  of  inestimable  practical  value 
to  the  surgeon  and  should  form  the  basis  of 
his  technique. 

We  know  that  a  malignant  neoplasm  does 
not  develop  anew,  but  that  cancer  cells  in  a 
number  of  possible  ways  have  been  left  intact 
in  the  organism  and  that  these  cells  serve  as 
a  nucleus  for  a  second  tumor.  The  cancer 
cells  migrating  from  the  original  tumor  may 
have  become  fixed  at  some  distance  from  the 
parent  cell,  and  the  new  tumor  due  to  these 
cells  may  be  separated  from  the  original 
w^ound  by  a  margin  of  healthy  tissue.  As  has 
been  previously  pointed  out,  cancer  cells 
migrate  principally  through  the  lymphatic 
and  venous  systems. 

Elsewhere  it  has  been  shown  that  cancer 
cells    disseminate    throughout    the    organism 


NATURE  43 

primarily  by  the  lymphatic  system.  A  dif- 
ferent growth  of  the  primary  tumor  may  ex- 
tend into  the  lymphatic  ducts  and  proliferate 
there,  checking  the  flow  of  the  lymph.  In 
the  removal  of  all  the  tissues  that  microscop- 
ically appears  to  be  diseased,  the  cells  that 
have  permeated  the  lymph  system  may  be  left 
intact  and  a  recurrence  will  follow  through 
these  remaining  cells.  Particular  attention, 
therefore,  must  be  given  in  surgical  technique 
not  alone  to  the  removal  of  the  tissue  that 
has  the  gross  appearance  of  a  cancer  growth, 
but  as  well  as  to  the  excision  of  all  tissue  in  the 
neighborhood  that  is  known  to  be  prone  to 
the  dissemination  of  cancer  cells,  and  this 
tissue  should  be  removed  as  widely  as  the 
anatomical  relations  to  other  parts  will  per- 
mit. This  fact  must  especially  be  borne  in 
mind  in  the  surgical  treatment  of  growths  in 
organs  or  tissues  that  have  a  rich  lymph  sup- 
ply, as,  for  instance,  the  breast.  By  means  of 
chains  of  lymphatic  nodes  the  breast  is  inti- 
mately connected  with  the  lymphatic  glands 
of  the  axilla,  the  supra-clavicular  glands,  the 
mediastinal  glands,  and  the  glands  of  the  op- 
posite breast.  Malignant  neoplasms  of  the 
breast  which  show  a  metastasis  to  any  of  these 
glands   may  be   considered   inoperable.      If, 


44  CANCER 

however,  the  case  is  operable,  not  only  the 
neoplasm,  but  the  entire  breast  with  the  fascia 
and  pectoral  muscles  must  be  excised  to  pre- 
vent a  recurrence  due  to  disseminated  intact 
cells.  Cancer  cells  spread  likewise  to  the 
venous  system.  If  a  growth  manifests  evi- 
dence of  hemorrhage,  in  all  probability  the 
growth  has  eroded  the  walls  of  the  vein.  The 
destruction  of  the  venous  wall  entails  the  en- 
trance of  malignant  cells  into  the  venous 
blood,  which  means  that  metastases  have  taken 
place  and  that  recurrence  will  follow,  due  to 
these  metastases.  Recurrence  may  be  due  also 
to  cells  dislodged  from  the  primary  tumor  by 
mechanical  manipulation,  and  this  is  particu- 
larly true  in  recurrence  within  the  serous 
cavities,  that  is,  within  the  thorax  or  the  peri- 
toneum. We  cannot  impress  too  strongly 
upon  the  physician  and  the  patient  the  risk 
following  undue  handling  of  malignant  tu- 
mors. The  therapeutic  measures  for  the  re- 
lief of  inflammatory  processes,  such  as  mas- 
sage and  rubbing,  should  never  be  employed 
where  the  tumor  is  suspected  of  being  can- 
cerous, and  the  examinations  of  such  growths 
should  be  undertaken  with  extreme  gentle- 
ness and  not  repeated  unless  absolutely  neces- 
sary.    Furthermore,  the  cancer  cells  may  be 


NATURE  45 

disseminated  by  incising  a  growth  to  obtain 
a  piece  of  tissue  for  examination.  At  times 
a  rapid  examination  of  the  tumor  by  the 
frozen  section  method  may  be  thought  ad- 
visable, although  positive  conclusions  cannot 
be  drawn  from  its  results.  In  cases  of  this 
kind,  when  practicable,  a  piece  of  tumor 
should  be  removed  by  cautery,  rather  than  by 
the  knife.  Authorities  who  have  had  expe- 
rience in  handling  cancer  patients  with  and 
without  operations  are  agreed  that  metastases 
in  recurrence  can  be  checked  more  rapidly  in 
patients  where  the  tumors  have  not  been  ex- 
cised or  cut  into  for  microscopical  examina- 
tion, than  in  cases  that  have  been  operat' 
upon.  It  would  seem,  therefore,  that  surgical 
interference — if  not  based  upon  an  intimate 
knowledge  of  the  means  by  which  cancer 
cells  disseminate,  causing  recurrence,  and  of 
the  methods  of  stimulating  cancer  cells  to 
proliferation — is  apt  to  be  ill-advised  and 
attended  with  unfortunate  results. 

Experimental  work  upon  the  transplanta- 
tion of  tumors  in  mice,  from  one  individual 
to  another,  have  shown  that  a  tumor  may  be 
produced  in  the  second  host  by  the  implan- 
tation of  intact  cells  subcutaneously.  There- 
fore, all  that  is  needed  to  produce  a  second 


46  CANCER 

tumor  is  an  inoculation  with  the  living  cells. 
Whether  cancer  may  be  transplanted  from 
one  human  being  to  another  in  a  similar  man- 
ner has  not  been  proved,  but  statistics  show 
that  the  growth  may  be  transferred  from  one 
locality  to  another  within  the  same  individual. 
As  applied  to  the  methods  for  treatment  of 
cancer,  observation  implies  that  cancer  cells 
coming  in  contact  with  other  organs  will  pro- 
duce secondary  tumors.  This  is  particularly 
true  of  sloughing  cancerous  tumors.  The 
roof  of  the  urinary  bladder  is  very  apt  to 
be  infected  from  a  cancer  at  its  base.  An  in- 
structive illustration  of  this  point  in  connec- 
tion with  another  portion  of  the  body  came 
under  the  observation  of  one  of  the  authors 
recently.  The  patient,  a  man  of  middle  age, 
complained  of  severe  penetrating  pain  in  the 
right  epigastric  region.  The  cause  of  the  pain 
was  diagnosed  by  the  surgeon  as  cholelithiasis. 
During  the  operation,  undertaken  without  a 
suspicion  of  a  malignant  neoplasm,  a  cancer 
was  found  in  the  upper  right  epigastric  re- 
gion. A  piece  of  tissue  was  removed  for 
examination,  and  the  wound  came  in  contact 
with  the  freshly  incised  growth.  When  it 
w^as  known  that  the  abdominal  growth  was 
malignant  the  wound  was  sutured  and  the 


NATURE  47 

patient  was  transferred  to  an  institution  de- 
voted exclusively  to  cases  of  cancer.  A  short 
time  after  his  entrance  a  growth  developed 
along  the  abdominal  scar  and  spread  very 
rapidly.  Moreover,  new  vigor  was  appar- 
ently given  to  the  intra-abdominal  growth, 
which  within  a  short  time  could  be  palpated 
with  ease;  and  at  autopsy  it  was  found  to  have 
invaded  the  small  intestines,  and  by  pressure 
upon  the  spinal  cord  to  have  produced  paral- 
ysis and  complete  anesthesia  of  the  lower 
extremities.  Further,  the  use  of  a  trocar  in 
tapping  or  exploring  malignant  tumors  is  in- 
variably productive  of  the  development  of 
secondary  tumors  along  the  line  of  entrance 
of  the  instrument.  The  greatest  number  of 
recurrences  due  to  implantation  of  cancer 
cells  in  healthy  tissue  are  reported  in  the  ex- 
cision of  malignant  growths  of  the  female 
genito-urinary  tract.  Cancer  of  the  uterus  is 
probably  the  most  common  form  of  the  mal- 
ady in  the  female  sex.  The  removal  of  the 
tumors  of  the  uterus  by  vaginal  hysterectomy 
is  frequently  followed  by  the  development  of 
the  tumor  in  the  scar  in  the  apex  of  the  va- 
gina, or  the  sides  of  the  vulva  (in  cases  of 
narrow  vaginal  orifice),  when  incisions  are 
made  at  these  points  to  afford  more  space  for 


48  CANCER 

the  removal  of  the  uterus.  It  is  practically 
impossible  to  keep  these  cut  surfaces  from 
touching  the  cancerous  growth  and  thus  to 
avoid  an  implantation  of  the  cancer  cells  in 
the  vagina.  The  use  of  the  cautery,  however, 
to  destroy  as  much  as  possible  of  the  growth 
before  its  removal,  although  it  does  not  ob- 
viate all  possibility  of  implantations,  never- 
theless may  diminish  the  chances  of  infection 
through  contact  of  living  cancer  cells  with 
healthy  tissues. 

The  cells  that  remain  in  the  wound  after 
excision  probably  proliferate  at  once.  How- 
ever, some  time  will  intervene  before  the 
presence  of  the  new  growth  can  be  demon- 
strated. The  time  that  must  elapse  without 
the  development  of  a  recurrence,  before  the 
case  can  be  considered  cured,  differs  accord- 
ing to  different  authorities.  Formerly  it  was 
considered  that  a  lapse  of  three  years  without 
a  recurrence  was  indicative  of  an  effectual 
cure.  Other  authorities  have  placed  the  limit 
at  two  years,  while  it  is  now  generally  ac- 
cepted that  recurrence  may  take  place  within 
five  years  (or  more)  of  the  operation. 

Ulceration  is  not  pathognomonic  of  malig- 
nant tumors,  and  therefore  as  a  diagnostic  sign 
it  has    little   value.     Innocent   tumors   may 


NATURE  49 

ulcerate  and  malignant  tumors  may  remain 
sterile.  Malignant  tumors  ulcerate  when  they 
are  exposed  to  injury  or  irritation,  and  in  this 
mechanical  production  of  the  ulceration  be- 
nign tumors  are  similar  to  the  malignant. 

A  peripheral  hyperplasia  with  a  central 
hypoplasia  leading  to  degeneration  is  charac- 
teristic of  a  rapidity  of  growth.  A  malignant 
tumor  depends  for  its  nourishment  not  upon 
special  vascular  and  lymph  supply  to  itself, 
but  principally  upon  the  blood  vessels  in  the 
stroma  of  the  tissue  invaded.  Hence  the 
periphery  of  the  tumor  receives  a  rich  sup- 
ply of  nutritive  material.  When,  however, 
the  blood  vessels  become  incorporated  in  the 
growth,  their  tissues  are  invaded  and  de- 
stroyed, which  means  that  the  central  portion 
of  the  tumor  degenerates  owing  to  a  failure 
of  nutrition.  The  degeneration  may  take  the 
form  of  an  active  necrosis,  or  the  form  of  a 
quiet  necrosis,  or  necrobiosis.  On  the  other 
hand,  sarcomata  may  undergo  a  calcareous 
degeneration  or  a  myxomatosis.  In  the  latter 
case  the  greater  portion  of  the  tumor  assumes 
a  jelly-like  appearance  and  is  surrounded  by 
a  thin  wall  of  tissue. 

Cachexia  is  not  invariably  present,  particu- 
larly in  sarcomatous  cases.     It  is  a  late  con- 


50  CANCER 

stitutional  development,  resulting  from  the 
effect  of  the  tumor  upon  the  organism  as  a 
whole.  The  time  of  the  development  of  the 
cachexia  depends  particularly  upon  the  loca- 
tion of  the  tumor.  Thus  a  neoplasm  of  the 
stomach  directly  interferes  with  the  supply 
of  nourishment  to  the  body,  so  that  the  ap- 
pearance of  the  cachexia  takes  place  in  the 
earlier  stages.  Peripheral  tumors,  however, 
for  instance,  of  the  breast,  may  attain  an 
enormous  size  before  the  patient  develops  a 
cachectic  appearance,  and  in  fact  the  cachexia 
may  never  take  place.  In  peripheral  tumors 
the  factors  that  play  the  greatest  part  in  pro- 
ducing the  cachexia  are  ulceration  of  the 
surfaces  with  hemorrhage  leading  to  a  septic 
condition.  Cachexia  due  to  carcinomata  that 
slough  rapidly  will  develop  more  rapidly 
than  in  any  other  conditions;  for  instance,  a 
carcinoma  of  the  cervix  of  the  uterus  is  char- 
acterized by  its  early  and  continuous  slough- 
ing. This  sloughing  may  be  the  cause  of  a 
secondary  infection  producing  the  cachexia. 
It  would  seem,  therefore,  that  in  treating  can- 
cer patients,  inasmuch  as  it  is  necessary  to 
stimulate  the  vitality  in  healthy  cells,  cachexia 
must  be  warded  off,  and  therefore  all  exter- 
nal tumors  or  growths  must  be  kept  from 


NATURE  51 

ulcerating.  This  applies  to  any  growth, 
whether  it  involves  the  cervix  of  the  uterus 
or  some  skin  manifestation.  As  to  the  means 
of  preventing  ulceration  and  secondary  infec- 
tion, see  chapter  on  Antiseptics.  The  cause 
of  the  cachexia  is  either  the  absorption  of 
catabolic  products  of  the  tumor  growth  and 
its  consequent  metastasis,  or,  secondarily,  the 
interference  exerted  by  the  tumor  upon  the 
functions  of  the  essential  organs.  The  entrance 
of  cancer  cells  into  the  blood  and  lymph  sys- 
tem takes  place  early,  and  a  general  dissemi- 
nation of  these  cells  can  be  detected  by  an 
analysis  of  the  blood  before  cachexia  devel- 
ops. A  degeneration  of  the  cancer  growth 
leads  to  a  secondary  infection,  and  the  effect 
of  this  upon  the  blood  stream  is  similar  to 
that  of  any  infection.  Our  observations  upon 
the  changes  in  the  composition  of  the  blood 
lead  us  to  believe  that  there  are  other  prod- 
ucts concerned  (of  which  little  is  known), 
that  find  their  way  through  the  tumor  into 
the  blood  stream,  and  these  products  may  be 
very  important  factors  in  the  etiology  of  the 
cachexia.  The  interference  exerted  by  the 
growth  upon  the  essential  organs  may  be  me- 
chanical, that  is,  due  to  pressure,  erosion  of 
its  walls,  and  so  on;  or  it  may  be  due  to  the 


52  CANCER 

absorption  of  toxic  products,  elaborated  by 
the  neoplasm. 

The  blood  changes  in  malignant  disease 
take  the  form  characteristic  of  a  secondary 
anemia,  varying  in  intensity.  The  produc- 
tion of  the  anemia  may  be  attributed  to  a 
number  of  causes,  principal  among  them  be- 
ing: (i)  the  action  of  the  toxic  products  of 
the  tumor  upon  the  organs  concerned  in 
blood  production;  (2)  secondary  infection; 
(3)  a  disturbance  of  the  organs  by  the  pri- 
mary growth  or  its  metastases.  Ordinarily 
the  red  cell  count  is  reduced.  Variations 
from  this  statement,  that  is,  a  normal  count 
or  an  increased  count,  must  be  attributed  to 
a  concentration  of  the  blood,  and  is  not  a  fa- 
vorable symptom.  The  percentage  of  hemo- 
globin is  subnormal,  and  this  may  take  place 
even  when  the  red  cell  count  is  normal.  The 
number  of  white  cells,  w^hen  increased,  usu- 
ally indicates  an  infection  rather  than  any 
characteristic  efifect  of  the  tumor.  Hemor- 
rhage and  rapid  growth  and  the  formation  of 
metastases  are  also  important  factors  in  pro- 
moting leukocytosis. 

The  cachexia  is  gradual  and  progressive. 
The  patient  assumes  a  straw-yellow  color, 
which  must  be  attributed  at  least  to  a  dimin- 


NATURE  53 

ished  hemoglobin  production  or  a  change  in 
the  composition  of  the  hemoglobin.  The  pain 
is  not  always  localized  in  a  growth  of  the 
gastro-intestinal  tract,  but  it  may  partake  of 
the  nature  of  what  Head  calls  ''Referred 
Pain."  Rheumatic  symptoms  give  rise  to 
what  has  been  called  rheumatic  diathesis. 
When  the  pains  are  due  to  an  ulceration  in 
the  secondary  infection,  they  are  more  potent 
in  producing  pain  than  the  growth  itself,  and 
therefore  there  is  every  need  of  keeping  the 
wound  clean.  In  non-ulcerated  cases  fever  is 
usually  absent,  or  there  may  be  a  slight  in- 
crease in  temperature  due  to  the  absorption 
of  toxic  products.  Some  of  the  cases  termi- 
nate in  coma.  The  majority,  however,  die  in 
a  condition  of  general  cachexia. 


CHAPTER    II 
Pre- Cancerous  Conditions 

The  overwhelming  percentage  of  recur- 
rence of  cancerous  lesions  following  opera- 
tive treatment  is  regretfully  attributed  by  the 
clinician  to  the  fact  that  the  malignant  nature 
of  the  lesion  is  recognized  too  late,  and  that 
when  it  comes  to  the  surgeon  it  has  already 
advanced  to  the  inoperable  stage.  Hence  the 
operative  treatment  of  neoplasms  is  far  from 
satisfactory.  In  this  direction  it  can  be  much 
improved. 

This  tendency  to  recur,  as  we  have  shown 
elsewhere,  is  characteristic  of  a  malignant 
neoplasm  and  due  to  its  ability  to  form 
metastases.  If,  therefore,  it  were  possible  by 
analytical  and  symptomatic  means  to  foretell 
the  development  of  a  malignancy,  or  the 
transformation  of  a  benign  into  a  malignant 
growth,  surgical  treatment  of  cancer  at  this 
stage  would  be  attended  with  much  greater 
success. 

The  recent  advances  in  pathology,  coupled 

54 


PRECANCEROUS  STATE  55 

with  the  careful  collection  of  statistics,  have 
rendered  possible  this  desired  end.  There  is 
no  phase  of  pathology  of  greater  profit  to  the 
general  clinician  and  surgeon  than  the  study 
of  the  so-called  pre-cancerous  lesions.  By  a 
pre-cancerous  lesion  we  understand  not  an 
incipient  cancer,  but  a  benign  lesion  or 
growth  of  the  type  that  most  frequently  de- 
velops malignant  characteristics.  Although 
such  a  lesion,  if  left  alone,  may  never  become 
a  cancer,  it  should  be  looked  upon  with  grave 
suspicion  by  the  surgeon. 

We  realize  that  in  making  the  above  state- 
ment we  are  simply  reiterating  what  has  been 
written  over  and  over  again,  particularly  in 
the  publications  of  the  last  ten  years;  but  the 
subject  is  such  an  important  one,  and  is  so 
forcibly  brought  to  the  attention  of  any  one 
who  studies  the  whole  cancer  problem  in  a 
serious  manner,  that  there  never  seems  to  be 
any  likelihood  of  the  statement  being  made 
too  often.  It  should  also  be  constantly  borne 
in  mind  that  statements  like  the  above  refer 
to  a  lesion  or  lesions  which  are  supposed  to 
be  clear  and  well-marked  entities,  and  that 
beyond  them  the  rest  of  the  system  is  free 
from  cancerous  invasion. 

Recent  works,  however,  through  new  meth- 


56  CANCER 

ods  of  technique  at  the  present  time  coming 
into  use  in  the  X-ray  laboratories,  the  new 
advances  made  in  the  chemical  examination 
of  the  urine  and  the  blood,  enable  us  to  clas- 
sify these  conditions  somewhat  more  clearly 
than  would  have  been  possible  ten  years  ago. 
They  can  be  classified  into  those  having  ex- 
ternal and  internal  lesions ;  they  may  also  be 
classified  into  those  where  the  whole  system, 
through  lack  of  time  or  opportunity  or  con- 
venience, has  not  been  as  thoroughly  exam- 
ined and  mapped  out  as  the  modern  methods 
of  diagnosis  would  admit.  A  second  class  in 
which,  the  presence  of  these  lesions  having 
been  observed,  a  thorough  and  systematic  in- 
vestigation of  the  whole  system  has  been 
made;  and  a  third  class,  which  we  may  be 
among  the  first  to  recognize,  which  may  be 
pre-cancerous,  in  which  no-  particular  lesion 
either  internal  or  external  can  be  diagnosed, 
but  in  which  there  is  a  bad  family  history  of 
the  frequency  of  cancer  occurrence,  and  in 
which  is  found  a  marked  modification  in  the 
sulphur  metabolism,  as  told  by  the  examina- 
tions of  the  blood  and  urine.  For  patients  of 
this  class  we  should  insist  on  examinations 
being  made  at  not  far  distant  intervals  from 
one  another,  and  the  necessity,  as  far  as  prac- 


PRECANCEROUS  STATE  57 

ticable,  of  such  individuals  leading  a  life 
where  the  tissue  metamorphosis  is  kept  in  as 
near  a  proper  condition  as  possible,  together 
with  the  administration  more  or  less  con- 
stantly of  internal  medication,  such  as  the 
indications  surrounding  any  individual  case 
would  seem  to  require.  This  is  referred  to 
again  in  the  chapters  on  treatment,  farther 
on.  Such  cases  are  very  apt  to  show  changes 
in  the  sulphur  metabolism  similar  to  those 
occurring  in  gout,  where  the  nitrogen  metab- 
olism is  alone  affected,  and  in  which  uric  acid 
is  the  prominent  characteristic  and  the  patient 
is  treated  accordingly,  but  in  members  of  the 
class  to  which  we  refer,  the  sulphur  and  not 
the  uric  acid  seems  to  be  the  element  the 
changes  in  the  metabolism  of  which  are  the 
most  prominent.  This,  too,  brings  us  to  a 
consideration  at  this  point  of  another  element 
which  is  apparently  more  or  less  involved  in 
the  changes  in  the  metabolism  due  to  cancer, 
and  that  is  potash.  An  able  treatise  has  been 
written  on  that  work  by  Ross,  "Cancer,  Its 
Genesis  and  Treatment,"  London,  1912;  and, 
recently,  one  by  Dr.  L.  Duncan  Bulkley, 
"Cancer,  Its  Cause  and  Treatment,"  has 
called  attention  to  changes  in  this  element. 
It  is  through  a  desire  to  dwell  more  carefully 


58  CANCER 

on  investigations  personally  carried  on  by  us 
that  the  changes  in  potash  metabolism  in  can- 
cerous conditions  are  not  more  frequently 
mentioned.  We  consider  them  of  less  im- 
portance than  the  sulphur;  but  later  on  we 
may  publish  our  observations  on  the  metab- 
olism of  potash. 

Referring  now  to  the  second  class — in  which 
some  lesion  has  been  observed  either  exter- 
nally or  internally,  and  in  which  a  careful 
examination  of  the  whole  system  has  been 
carried  on — among  the  lesions  occurring  in 
this  class  may  be  mentioned  apparent  fibrous 
tumors  of  the  breast  or  of  the  uterus,  old 
chronic  inflammatory  conditions  of  the  pros- 
tate, ulcers  of  the  stomach,  and  on  the  skin  or 
mucous  membrane  such  lesions  as  frequently 
recurring  herpes,  and  patches  of  chronic 
seborrhoea,  or  eczema.  These  should  all  be 
treated  by  excision.  X-ray,  or,  according  to 
conditions  surrounding  any  given  case,  by 
proper  measures,  either  local  or  general,  to 
do  away  with  any  chronic  inflammatory  proc- 
ess that  may  be  present. 

There  still  remain  those  cases  of  the  first 
class  mentioned,  in  which  chronic  lesions 
exist  which  may  become  cancerous,  but  on 
account  of  various   reasons   it  is  practically 


PRECANCEROUS  STATE  59 

impossible  for  the  attendant  to  use  all  the 
refinements  of  diagnosis  which  might  in  other 
cases  be  available.  Under  such  circumstances 
the  attendant  should  carry  out  as  many  of 
these  refinements  as  possible,  according  to  the 
circumstances  surrounding  any  given  case. 
The  above  statement  is  so  simple  that  it  hardly 
seems  necessary  to  dwell  on  it,  but  clinical 
experience  seems  to  indicate  that  even  at  the 
present  time  thorough  diagnostic  measures, 
even  when  available,  are  not  employed  as 
frequently  as  they  should  be. 

To  illustrate:  If  a  small  tumor  of  the 
breast  presents  itself,  and  it  is  impossible  to 
obtain  careful  X-ray  pictures  taking  in  the 
thorax,  the  liver,  the  stomach,  and  the  gall 
bladder,  at  least  a  careful  examination  can 
be  made  of  the  urine  and  the  blood,  particu- 
larly as  regards  the  sulphur  content,  and  the 
prognosis  before  operation  modified  some- 
what according  to  the  conditions  that  may  be 
found.  Even  from  careful  examination  of 
these  not  only  will  it  be  possible  to  modify 
the  prognosis,  but  the  results  of  such  findings 
may  often  have  some  modifying  efiPect  upon 
the  nature  or  extent  of  the  procedures,  opera- 
tive or  otherwise,  to  be  undertaken. 


PART    III 
DIAGNOSIS    OF    CANCER 

CHAPTER    I 

Details  of  Methods  of  Sulphur  Find- 
ings IN  Blood  and  Urine 

The  blood  as  a  circulating  fluid  comes  into 
intimate  contact  with  the  cells  of  all  the  tis- 
sues and  organs,  and  between  the  blood  and 
the  cells  there  is  an  exchange  of  nutritive 
material  and  catabolic  products.  We  would 
expect,  then,  that  the  products  from  any  par- 
ticular abnormality  would  find  their  way  into 
the  blood  stream,  and  there  could  be  detected. 
The  blood  of  cancer  patients  shows  concen- 
tration of  constituents  that  are  not  paralleled 
by  any  other  pathological  condition.  Now, 
gout  is  characterized  by  an  increase  of  the 
uric  acid  content  of  the  blood.  Chronic  in- 
terstitial nephritis  produces  an  increase  in  the 
urea,  uric  acid,  and  creatinin  of  the  blood. 
Diabetes,  on  the  contrary,  does  not  affect  the 

60 


SULPHUR   FINDINGS  6l 

nitrogenous  constituents,  but  is  characterized 
by  an  increase  of  the  sugar  content.  None  of 
the  constitutional  pathological  lesions  thus  far 
studied  produce  any  effect  that  can  be  simu- 
lated by  that  of  the  malignant  tumor.  A  ma- 
lignancy in  all  the  cases  examined  has  pro- 
duced an  increase  in  the  non-protein  nitrogen, 
which  increase  cannot  be  accounted  for  by 
any  increase  in  urea,  uric  acid,  or  creatinin; 
nor  is  it  an  amino-nitrogen  compound. 

Diseases  of  the  liver  that  interfere  with 
the  activities  of  this  organ  will  present  an 
increase  of  the  amino-nitrogen,  owing  to  the 
fact  that  the  liver  no  longer  can  deaminize 
amino  acids.  Further,  carcinomata  manifest 
an  increase  in  the  total  sulphur  content  of  the 
blood.  In  these  conditions  the  proportion 
between  the  non-oxidized  and  the  oxidized 
sulphur  of  the  blood  stream  is  disturbed  with 
a  proportionate  increase  of  the  former. 

Methods  Used  for  Analysis  of  the  Blood 

The  total  non-protein  sulphur  of  the  blood 
in  non-carcinomatous  conditions  may  be 
stated,  from  our  observations,  to  be  an  aver- 
age of  3.6  milligrams  per  100  c.c.  of  blood. 
Now,  of  this  total  sulphur  some  80  per  cent 
to  85  per  cent  is  in  the  form  of  sulphates. 


62  CANCER 

The  remainder  is  non-oxidized  sulphur.  In 
carcinomatous  conditions  the  total  non-protein 
sulphur  rises  to  two  or  three  times  the  normal 
figure,  while  the  total  sulphates  remain  at 
the  normal  level.  It  appears,  then,  that  the 
increase  in  sulphur  is  due  to  an  increased 
amount  of  non-oxidized  sulphur  in  the  blood, 
not  due,  however,  to  the  proteins. 

For  the  methods  of  calculating  the  non- 
protein nitrogen,  non-protein  sulphur,  urea, 
uric  acid,  and  creatinine  of  the  blood  we  refer 
the  reader  to  reliable  text-books  on  the  chem- 
istry of  the  blood. 

Concerning  the  urine,  all  previous  investi- 
gations conducted  upon  the  question  of  sul- 
phur metabolism  in  cancer  conditions  have 
utilized  the  Salomon-Saxl  reaction  for  neu- 
tral sulphur  in  the  urine.  This  consists  in 
converting  the  ethereal  sulphates  in  the  urine 
by  boiling  with  hydrochloric  acid  into  inor- 
ganic sulphates  and  then  precipitating  the 
total  sulphates  with  barium  chloride,  the  fil- 
trate from  this  reaction  containing  the  unoxi- 
dized  sulphur.  To  the  total  filtrate  hydrogen 
peroxide  was  added  and  the.  mixture  boiled 
and  then  upon  standing  the  precipitate  was 
thrown  down,  which  precipitate  represented 
the  total  neutral  sulphur  in  the  form  of  sul- 


SULPHUR  FINDINGS  63 

phate.  This  precipitate  was  allowed  to  settle 
out  in  a  conical  graduated  tube,  and  from  the 
amount  of  precipitate  formed  a  positive  or  a 
negative  reaction  was  reported.  A  most  con- 
scientious and  comprehensive  account  of  this 
method,  with  a  very  complete  bibliography 
of  the  subject,  has  recently  been  published  by 
Max  Kahn,  Journal  of  Cancer  Research^ 
July,  1917. 

Kahn's  conclusions,  as  given  in  the  article 
referred  to  above,  are  as  follows:  ^'In  car- 
cinoma there  is  generally  observed  an  in- 
crease in  the  percentage  of  neutral  sulphur 
in  the  urine.  This  may  be  ascribed  to  a 
lessened  power  of  oxidation  or  to  an  increased 
destruction  of  tissue  with  the  failure  of  the 
organism  to  oxidize  the  broken-down  prod- 
ucts to  the  sulphate  (oxidized)  state.  The 
colloidal  nitrogenous  substances  are  increased 
in  the  urine  of  cancer  patients,  as  well  as  in 
the  urine  of  anemic,  diabetic  and  syphilitic 
individuals,  etc.  It  has  been  the  experience 
of  the  author  (Kahn)  that  the  determination 
of  this  fraction  in  conjunction  with  the  Salo- 
mon-Saxl  test  for  so-called  'neutral  sulphur' 
is  of  great  aid  in  the  diagnosis  of  carcinoma 
if  both  of  these  tests  are  positive.  A  nega- 
tive  result  with   either   the   Salkowski-Kojo 


64  CANCER 

test  or  the  Salomon-Saxl  test  detracts  very 
much  from  the  significance  of  the  results  so 
far  as  carcinoma  is  concerned." 

Some  of  our  own  cases  have  also  shown,  in 
addition  to  the  excess  of  neutral  sulphur,  an 
excess  in  the  nitrogen  products  in  the  urine. 
But  we  do  not  consider  this  latter  so  much 
indicative  of  carcinoma  as  of  nephritis,  which 
may  or  may  not  be  the  result  of  the  carcinoma. 

Our  own  investigations  into  the  sulphur 
metabolism  in  carcinomatous  conditions  at 
first  were  based  upon  the  Salomon-Saxl  reac- 
tion, but  it  was  found  that  this  reaction  was 
unreliable,  because  in  all  conditions  the  hy- 
drogen peroxide  did  not  completely  oxidize 
the  neutral  sulphur;  and,  moreover,  it  was 
found  difficult  to  obtain  a  sample  of  hydro- 
gen peroxide  which  did  not  contain  an  im- 
purity that  would  give  a  precipitate  with  the 
barium  chloride.  We  therefore  adopted  the 
Benedict  method  for  total  sulphur  and  the 
Folin  technique  for  the  total  and  inorganic 
sulphates. 

Total  Sulphur. — To  lo  c.c.  of  urine  are 
added  5  c.c.  of  the  Benedict  sulphur  reagent 
in  an  evaporating  porcelain  dish.  The  mix- 
ture is  carefully  heated  until  it  solidifies,  and 
is  then  heated  to  the  maximum  intensity  of 


SULPHUR   FINDINGS  65 

the  Bunsen  burner  for  ten  minutes  until  it 
becomes  completely  black.  After  the  dish  has 
cooled,  this  black  residue  is  dissolved  in  20 
c.c.  of  1-4  hydrochloric  acid,  and  10  c.c.  of 
10  per  cent  barium  chloride  are  added.  The 
precipitate  is  filtered  oflf  in  a  Gooch  crucible 
or  through  filter  paper  and  very  carefully 
washed,  and  the  amount  of  precipitate  is  de- 
termined by  ashing  and  weighing. 

For  the  Sulphur. — The  urine  is  first  diluted 
with  an  equivalent  amount  of  1-4  hydro- 
chloric acid.  For  this  purpose  one  takes  25 
c.c.  of  urine,  and  after  boiling  for  twenty  to 
thirty  minutes,  the  mixture  is  cooled  and 
water  added  to  150  c.c,  then  10  c.c.  of  5  per 
cent  barium  chloride.  The  precipitate  is  fil- 
tered and  weighed  as  for  the  neutral  sulphur. 

Inorganic  Sulphates. — To  25  c.c.  of  urine 
are  added  20  c.c.  of  1-4  hydrochloric  acid  and 
the  volume  made  up  to  150  c.c.  with  water. 
Then  5  c.c.  of  5  per  cent  barium  chloride  are 
added  and  the  precipitate,  after  at  least  one 
hour  settling,  is  filtered  ofif  and  weighed. 

These  methods  give  the  compounds  of  the 
sulphur  content  of  the  urine  as  grams  of  SO3, 
and  knowing  the  total  volume  of  urine,  it  is 
best  to  express  the  output  of  sulphur  as  the 
amount  excreted  in  twenty-four  hours.     The 


66  CANCER 

total  sulphur  minus  the  total  sulphates  gives 
the  total  neutral  sulphur.  If  it  is  desired  to 
divide  the  neutral  sulphur  into  two  groups, 
the  easily  oxidized  and  the  difficultly  oxi- 
dized group,  one  should  take  the  filtrate  from 
the  total  sulphates,  evaporate  that  down  over 
a  water  bath  to  about  25  c.c,  and  then  add 
10  c.c.  of  ferric  chloride,  and  heat  over  a  free 
flame  for  fifteen  minutes.  The  additional 
sulphur  obtained  by  this  technique  over  the 
total  sulphates  represents  the  total  neutral 
sulphur  in  the  easily  oxidized  group.  By 
subtracting  the  inorganic  sulphates  from  the 
total  sulphates  we  obtain  the  ethereal  sul- 
phates. Subdividing  the  neutral  sulphur  into 
two  groups  enables  us  to  say  whether  the  liver 
is  involved  in  a  carcinomatous  condition  or 
not.  It  is  the  function  of  the  liver  to  dilute 
the  taurine  into  taurocholic  acid  which,  com- 
bined with  sodium  and  potassium,  is  excreted 
in  the  bile.  A  lesion  of  the  liver  of  such  an 
extent  as  to  inhibit  the  functions  of  that  organ 
will  necessarily  imply  that  the  taurine  will 
not  be  synthesized  into  the  corresponding 
acid,  and  therefore  it  will  not  be  removed 
from  the  blood  stream.  In  such  a  condition 
an  abnormal  quantity  of  taurine  will  pass  into 
the  urine.    This  will  mean  an  increase  in  the 


SULPHUR   FINDINGS  67 

neutral  sulphur  and  an  increase  in  the  diffi- 
cultly oxidized  group,  whereas  in  carcinoma 
we  find  an  increase  in  the  easily  oxidized 
group.  Too  much  stress,  however,  should  not 
be  placed  upon  the  distinction,  because  a  car- 
cinoma of  any  extent  will  form  metastases  in 
the  liver  and  thus  interfere  with  the  problems 
of  its  function. 

Urinary  Sulphur. — In  the  chemical  inves- 
tigations of  metabolism,  workers  have  gen- 
erally confined  their  attention  to  the  nitrog- 
enous constituents  of  the  urine;  the  sulphur, 
however,  demands  equal  consideration.  The 
sulphur  occurs  in  the  urine  in  two  forms,  the 
oxidized  sulphur,  which  is  composed  of  the 
inorganic  sulphates  and  the  organic  sulphates, 
and  the  unoxidized  sulphur,  composed  of  a 
number  of  constituents  that  are  divided  into 
two  groups.  Of  the  first,  the  easily  oxidized 
group,  cystine  and  potassium  sulpho-cyanate 
are  typical  examples;  of  the  difficultly  oxi- 
dized group,  taurine  is  the  salient  component. 
The  unoxidized  group  is  more  commonly 
known  as  the  neutral  sulphur.  Folin  has 
shown  that  the  oxidized  group  consists  of 
products  of  exogenous  metabolism,  while  the 
neutral  sulphur  contains  the  products  of  en- 
dogenous metabolism,  that  is,  of  tissue  break- 


68  CANCER 

down.     The  neutral  sulphur,  then,  would  be 
comparable   to   the   nitrogen  of   endogenous 
nitrogenous  products,  as  creatinine,  creatine, 
etc.    Our  own  experiments  upon  feeding  pa- 
tients with  sulphur-containing  foods  and  sul- 
phur-free foods  has  shown  that  the  amount  of 
neutral  sulphur  is  independent  of  the  sulphur 
content  of  the  diet.     The  urine  of  carcinom- 
atous cases  is  characterized  by  the  fact  that 
they  show  an  increase  in  the  neutral  sulphur 
compared  to  the  oxidized  sulphur,  but  the 
total  amount  of  sulphur  excreted  is  dimin- 
ished.    Under  normal   conditions,   a  person 
engaged  in  moderate  activity  excretes  about 
3   grams  of  total  sulphur  estimated  as  SO3 
in  twenty- four  hours.     Of  this,  5  to  13  per 
cent  is  composed  of  neutral  sulphur,  about 
equally  divided  between  the  easily  oxidized 
and  the  difficultly  oxidized  groups.     Of  the 
oxidized    sulphur    the    inorganic    sulphates 
stand  to  the  organic  sulphates  in  the  ratio  of 
10  to   I.     This  balance  between  the  sulphur 
components  is  disturbed  in  carcinoma.     The 
total  excretion  of  sulphur  drops  to  below  2 
grams  in  twenty-four  hours.    The  proportion 
of  neutral  sulphur  is  increased  to  from  20 
to  30  per  cent,  or  even  higher,  of  the  total 
sulphur.    The  relative  amount  of  neutral  sul- 


SULPHUR  FINDINGS  69 

phur  is  not  influenced  by  the  sulphur  content 
of  the  diet.  However,  X-ray  treatment,  as 
long  as  a  growth  is  submitted  to  the  emana- 
tion, greatly  increases  the  output  of  neutral 
sulphur,  but  this  returns  again  to  its  former 
level  when  the  treatment  has  ceased.  So,  too, 
the  surgical  removal  of  the  growth  is  appar- 
ently accompanied  by  a  proportionate  drop 
in  the  amount  of  neutral  sulphur  excreted. 
With  the  data  at  our  disposal  we  are  con- 
vinced of  the  invariability  of  these  findings. 
But,  however,  the  data  will  not  permit 
speculation  at  the  present  time,  regarding  the 
nature  of  the  chemical  changes  in  a  carci- 
nomatous cell  the  cytoplasm  predominates  in 
amount  over  the  nucleus,  and  consequently 
inasmuch  as  sulphur  proteins  predominate  in 
the  cytoplasm  we  would  expect  an  increased 
output  of  endogenous  sulphur  metabolic 
products.  At  the  present  time  plans  are  be- 
ing made  for  a  histo-chemical  study  of  the 
changes  in  tumor  growth,  and  it  is  hoped  that 
these  investigations  will  throw  more  light 
upon  the  origin  and  the  significance  of  the 
increased  neutral  sulphur  output.  However, 
at  the  present  tifne  these  findings  have  been 
sufficiently  substantiated  to  constitute  a  valu- 
able aid  in  diagnosis. 


70  CANCER 

After  the  removal  of  a  malignant  tumor, 
it  has  been  noted  that  the  non-protein  nitro- 
gen and  the  sulphur  return  to  their  normal 
level.  It  would  seem,  therefore,  that  they  are 
directly  the  products  of  the  tumor  metab- 
olism, and  not  products  of  the  effect  of  the 
tumor  upon  the  general  system,  as  in  cachexia. 
The  exact  chemical  nature  of  the  compound 
or  compounds  whose  occurrence  in  the  blood 
gives  rise  to  this  abnormal  amount  of  nitro- 
gen and  sulphur  is  at  the  present  time  an 
unsolved  problem,  but  we  are  justified  in 
considering  the  same  as  a  metabolic  product 
of  the  tumor  growth,  or  a  toxin  invading  the 
general  circulation,  and  thus  causing  metas- 
tases. It  would  seem,  therefore,  that  if  this 
product  be  a  toxin  predisposing  other  tissue 
cells  or  other  hosts  to  a  malignant  formation, 
the  inoculation  of  other  individuals  with  the 
carcinomatous  blood  would  give  rise  to  tumor 
formation  in  the  new  hosts.  It  has  been  found 
that  in  animal  experimentation  this  fact  has 
not  been  substantiated.  However,  we  must 
not  go  too  far  in  our  deductions  from  animal 
experimentations,  because  it  has  been  found 
that  animals  will  not  always  develop  consti- 
tutional lesions  characteristic  of  the  human 
organism.     Moreover,  if  this  compound  be  a 


SULPHUR   FINDINGS  71 

predisposing  toxin,  then  carcinomata  may  be 
inherited,  in  a  loose  sense  of  the  word;  that 
is,  the  toxin  may  pass  from  the  placental  to 
the  foetal  circulation,  predisposing  the  foetus 
to  a  malignant  tumor  formation  at  the  in- 
tervention of  the  secondary  cause.  Such  a 
conception  coincides  with  observations  upon 
carcinomata  transmission  in  breeding  mice. 
(See  chapter  on  Heredity.)  By  successive 
breeding  with  aliens,  that  is,  with  non-infected 
animals,  the  vitality  of  the  toxin  may  be 
greatly  decreased,  and  consequently  may  be 
entirely  bred  out. 


CHAPTER   II 

Diagnosis  by  Chemical  and  Bacteriolog- 
ical Means 

The  general  statement  frequently  made  by 
the  surgeon,  that  every  neoplasm,  whether 
malignant  or  benign,  should  be  removed  sur- 
gically, deserves  serious  consideration.  It  is 
indeed  true  that  every  tumor,  whose  surgical 
removal  would  not  interfere  with  the  func- 
tions of  any  vital  organ,  may  be  excised  with 
impunity.  However,  inasmuch  as  the  treat- 
ment of  cancer  should  not  end  with  the  ex- 
cision of  the  tumor,  there  is  every  need  to 
carefully  diagnose  a  malignancy,  and  upon 
a  positive  diagnosis  to  institute  an  anti-car- 
cinomatous  or  anti-sarcomatous  treatment. 
Many  pathologists  look  upon  neoplasms  as 
potentially  malignant,  and  therefore  advise 
their  removal.  However,  where  we  have  an 
involvement  of  a  vital  organ,  excision  becomes 
impossible,  and  we  must  resort  to  all  the 
means  at  our  disposal  to  substantiate  the  ex- 
istence of  a  malignant  neoplasm.    Moreover, 


LABORATORY  DIAGNOSIS  73 

inasmuch  as  the  treatment  of  cancer  is  largely 
prophylactic,  an  early  diagnosis  is  very  essen- 
tial. Where  the  growth  is  not  removed  by 
surgical  means,  we  cannot  apply  a  means  of 
diagnosis  based  upon  the  morphological  char- 
acter of  the  cells,  but  we  are  forced  to  adopt 
chemical,  and  in  some  cases  bacteriological, 
methods  for  the  corroboration  of  the  clinical 
findings. 

Neoplasms  of  the  Gastric  Intestinal 
Tract 

Stomach. — The  work  heretofore  done  by 
pathologists  and  surgeons  in  connection  with 
the  cases  of  gastric  cancer  which  have  been 
cured,  or  have  resulted  in  any  considerable 
prolongation  of  life,  has  only  been  possible 
in  those  cases  in  which  an  early  diagnosis  was 
made,  thus  permitting  a  removal  of  the  neo- 
plasm before  it  had  become  an  extensive 
process.  In  gastric  conditions  we  are  pre- 
sented with  the  problem  of  differentiating  a 
malignant  neoplasm  from  such  conditions  as 
gastric  ulcer,  chronic  dilatation  of  the  stom- 
ach, chronic  gastritis — conditions  which  in 
many  ways  closely  simulate  a  malignant 
tumor. 


74  CANCER 

General  Considerations. — ^When  a  gastric 
malignancy  has  become  thoroughly  estab- 
lished in  the  general  appearance  of  the  pa- 
tient, there  is  the  appearance  of  hopelessness 
characterized  by  a  dullness  of  the  eye,  sunken 
cheeks,  and  listless  posture,  with  a  tendency 
to  collapse  upon  any  physical  exertion.  In 
addition  to  these  there  will  be  noted  a  loss  of 
weight,  scaly  skin,  an  absence  of  fatty  depos- 
its about  the  body,  and  a  scaphoid  appearance 
about  the  abdomen.  The  general  picture  re- 
sembles that  of  anemia,  with  a  grayish  or  yel- 
lowish tan  coloration  of  the  skin.  The  mucous 
surfaces  of  the  mouth  are  pale  and  parched. 
The  tongue  becomes  heavily  coated  and  shows 
well-marked  fissures  and  papillae,  and  the 
breath  has  the  odor  of  gastric  fermentation. 
Decayed  teeth  and  pyorrhoea  alveolaris  are 
not  infrequently  found  to  accompany  the 
gastric  malignancy.  The  mouths  of  such 
patients  usually  contain  parasites,  chief  among 
which  are  amoebae  and  pathogenic  bacteria. 
In  the  late  stages  of  the  disease  edema  will 
sometimes  occur  beneath  the  eyes.  The  fer- 
mentation in  the  stomach  gives  rise  to  a 
growth  of  multitudes  of  micro-organisms, 
which  will  be  taken  up,  and  on  their  passage 
through    the    kidney    produce    a    secondary 


LABORATORY  DIAGNOSIS  75 

chronic  nephritis.  Externally  there  may  be 
evidence' of  metastases  in  the  lymph  glands, 
particularly  in  the  left  supra-clavicular  space. 
Metastases  in  the  abdominal  cavity  give  rise 
to  ascites,  and  the  composition  of  the  fluid 
may  be  characteristic  of  this  disease.  The 
liver  may  be  enlarged,  owing  to  secondary 
growths.  Patients  with  gastric  malignancies 
very  frequently  manifest  nervousness,  which 
in  most  cases  is  concerned  with  their  great 
loss  in  weight,  deficiency  of  strength,  and  the 
inability  to  take  food. 

In  6  per  cent  of  the  cases  the  neoplasm  has 
been  found  to  involve  the  pylorus,  the  antrum, 
and  the  lesser  curvature.  The  posterior  wall 
has  been  involved  in  about  9  per  cent  and 
the  anterior  wall  in  about  2  per  cent. 

Chemical  Examination.— The  chemical  fea- 
tures of  the  gastric  secretion  are  not  sufficient 
to  serve  as  a  basis  for  a  positive  diagnosis,  but 
combined  with  the  clinical  history  they  make 
an  invaluable  aid  in  establishing  or  excluding 
the  presence  of  a  malignancy. 

The  most  salient  factor  of  the  gastric  se- 
cretion in  this  condition  is  the  absence  of  free 
hydrochloric  acid.  This,  however,  is  not 
characteristic  alone  of  carcinoma,  inasmuch 
as  it  is  found  also  in  atrophic  and  chronic 


76  CANCER 

gastritis.  It  has  been  suggested  that  the  ab- 
sence of  the  hydrochloric  acid  is  due  to  the 
combination  of  this  acid  with  a  compound 
secreted  from  the  malignant  growth.  From 
a  number  of  cases  that  we  have  followed,  it 
is  interesting  to  note  that  very  frequently  the 
absence  of  free  hydrochloric  acid  is  accom- 
panied by  diminished  content  of  the  blood. 

Acid  Constituents. — Before  an  estimation 
of  the  acidity  is  made,  the  gastric  contents 
should  be  filtered.  For  the  free  acidity  we 
use  2  c.c.  of  the  fluid  titrated  against  N/50 
sodium  hydroxide  with  Topfer's  solution  as 
an  indicator.  For  the  total  acidity  phenol- 
phthalein  is  employed,  titrating  the  same 
quantity  of  contents  with  alizarin  as  an  in- 
dicator, and  subtracting  this  from  the  total 
acidity  against  the  combined  acidity. 

For  the  examination  of  the  gastric  contents 
the  earlier  investigators  employed  the  Ewald 
test  meal  and  the  retention  meal.  A  meal 
consisting  of  two  slices  of  bread,  unbuttered, 
or  dry  toast  were  given  to  the  patient  with 
200-300  c.c.  of  fluid,  water  or  unsweetened 
tea.  One  hour  afterwards  the  total  contents 
of  the  stomach  were  aspirated  and  the  con- 
tents analyzed  for  the  various  components  of 
the  acidity,  the  presence  of  blood,  and  the 


LABORATORY  DIAGNOSIS  77 

peptic  activity.  These  analyses  furnished  the 
clinician  with  an  idea  of  the  secretory  func- 
tions of  the  stomach.  The  motility  of  the 
organ  was  determined  by  giving  a  meal  con- 
taining articles  of  food  poorly  digested,  such 
as  raisins,  and  twelve  hours  afterwards  re- 
moving the  total  contents  of  the  stomach. 
Under  these  conditions  only  an  inaccurate 
idea  of  the  stomach's  secretory  or  motor  pow- 
ers can  be  secured.  Moreover,  these  tests  are 
accompanied  by  great  distress  to  the  patient, 
and  inasmuch  as  these  types  of  cases  are  al- 
ready in  a  very  weakened  condition,  we  would 
not  advise  these  means  of  chemical  diagnosis. 
The  method  which  in  our  hands  has  yielded 
the  best  results  is  as  follows.  The  evening 
before  the  test  is  to  be  performed  a  duodenal 
tube  is  swallowed.  The  patient  lies  upon  the 
left  side,  until  it  is  judged  that  the  tube  has 
entered  the  stomach.  Thereupon  the  patient 
lies  upon  his  back,  and  then  upon  his  right 
side.  The  following  morning  it  will  be  found 
that  the  tube  has  entered  the  duodenum.  This 
will  be  indicated  by  the  golden  yellowish  ap- 
pearance of  the  fluid  aspirated  and  its  alkaline 
reaction  to  congo  red.  Immediately  before 
the  performance  of  the  test  another  tube  is 
dropped,    with    the   patient   sitting   upright. 


78  CANCER 

The  swallowing  of  the  tube  may  be  assisted 
by  the  ingestion  of  a  small  quantity  of  water. 
About  200  c.c.  of  water  are  given  to  the  pa- 
tient, and  a  portion  of  the  contents  of  the 
stomach  and  duodenum  removed  by  a  syringe 
for  fifteen  minutes,  until  the  stomach  is  emp- 
tied. The  fluid  thus  obtained  is  analyzed  for 
its  acidity,  enzyme  activity,  and  for  the  pres- 
ence of  food  remains  or  pathological  constitu- 
ents, such  as  blood  or  carcinomatous  cells. 

If  the  pylorus  is  patent,  the  duodenal  tube 
will  easily  enter  the  small  intestines.  In  cases 
of  pyloric  stenosis  the  duodenal  tube  may  be 
dispensed  with. 

The  Microscopic  Appearance  of  the  Re- 
tention Contents. — To  obtain  the  retention 
contents  of  the  stomach  the  total  fluid  in  the 
stomach  is  removed  before  the  giving  of 
water.  This  is  done  by  removing  the  contents 
while  the  patient  lies  upon  the  right  side,  then 
upon  the  back,  and  finally  upon  the  left  side. 
If  the  pylorus  is  not  obstructed  the  retention 
contents  will  be  clear.  It  may  vary  in  vol- 
ume from  a  few  cubic  centimeters  to  a  liter; 
frequently  portions  of  poorly  digested  food 
will  be  removed,  intermixed  with  mucus.  If 
blood  is  present'  the  aspirated  fluid  will  be 
dark    brow^n    or    coffee    color.      Not    infre- 


LABORATORY  DIAGNOSIS  79 

quently  a  discoloration  due  to  bile  will  be 
obtained.  In  the  majority  of  cases  the  fluid 
will  have  a  rancid  odor,  due  to  volatile  or- 
ganic acids.  Putrefactive  odors  may  be  due 
to  a  sloughing  of  the  cancer  tissue,  or  the 
breaking  down  of  blood,  or  the  penetration 
of  foreign  material  through  a  fistula.  Mucus, 
in  a  tough,  stringy  form,  containing  particles 
of  food,  or  the  cancer  tissue  will  be  easily 
obtained.  Where  the  mobility  of  the  stom- 
ach is  very  low,  and  the  free  acid  deficient, 
the  food  particles  will  be  in  large  amounts 
and  poorly  digested. 

In  spite  of  the  clinical  symptoms  mentioned 
above  as  regards  the  appearance  of  the  pa- 
tient, loss  of  weight  and  appetite,  extensive 
cancer  infiltrations  of  the  stomach,  intestines, 
and  both  are  occasionally  met  with  at  opera- 
tion, where  the  general  appearance  of  the 
patient  presents  no  difference  from  that  of 
perfect  health.  Such  cases  may,  however, 
give  a  history  of  having  very  recently  had 
symptoms  of  intestinal  irregularities  of  some 
sort,  justifying  the  surgeon  in  performing  an 
immediate  exploratory  operation,  as  the 
symptoms  may  simulate  gall  bladder  disease 
or  appendicitis.  It  would  be  extremely  inter- 
esting to  note  in  these  cases  whether  sulphur 


8o  CANCER 

examination  of  the  urine  and  blood  would  not 
show  an  increase  in  the  percentage  of  neutral 
sulphur,  as  we  believe  would  be  the  case.  So 
far  we  have  not  had  an  opportunity  to  verify 
this  statement.  The  type  of  case  just  men- 
tioned is  comparatively  rare. 


CHAPTER    III 

Diagnosis  of  Malignancies  of  the 
Stomach 

The  problem  presented  in  diagnosis  of  a 
malignant  growth  of  the  stomach  is  to  dif- 
ferentiate such  a  condition  from  an  anacid 
gastritis  that  is  of  the  interstitial  or  paren- 
chymatous type  and  a  gastric  ulcer.  It  may 
be  said  that  gastric  cancer  is  found  prin- 
cipally in  individuals  of  advanced  age  who 
give  no  history  of  chronic  dyspepsia.  This 
is  most  probably  due  to  the  fact  that  a 
chronic  dyspeptic  assiduously  avoids  food  of 
a  quality  that  is  indigestible,  or  of  a  quantity 
beyond  the  capacity  of  the  gastric  digestion, 
and  therefore  the  irritating  action  of  indiges- 
tible food  or  of  chronic  overeating  is  obvi- 
ated. 

Gastric   malignancies    are    observed    more 

frequently   in    individuals   with    the   normal 

habitus   than   in   individuals   with   a  habitus 

enteroptoticus.     The  onset  of  the  disease  is 

more  rapid  and  more  acute  than  in  gastritis 

8i 


82  CANCER 

and  more  persistent  than  in  ulcer.  The 
pain  associated  with  this  condition  is  spon- 
taneous and  is  found  to  be  independent  of 
the  intake  of  food.  It  is  referred  to  the 
epigastrium  and  is  generally  described  as  a 
gnawing  or  boring  sensation.  The  vomiting 
of  the  stomach  contents  after  eating  is  a  fre- 
quent, but  not  always  a  characteristic  sign, 
p?  Etiology. — Gastric  carcinoma  is  more  fre- 
quently observed  in  men  than  in  women.  In 
men  the  most  frequent  cause  is  alcoholism. 
In  both  sexes  chronic  overeating  or  the  in- 
take of  food  difficult  of  digestion  may  be  a 
sufficient  secondary  cause  to  invoke  a  malig- 
nancy. In  a  small  percentage,  patients  with 
gastric  cancer  give  a  previous  history  of 
ulcer.  Trauma,  particularly  of  the  character 
associated  with  occupational  diseases,  may 
lead  to  a  malignant  formation.  If  the  onset 
of  the  gastric  affection  can  be  definitely  dated 
within  a  year  or  eighteen  months  following 
injury,  it  is  safe  to  say  that  the  etiological 
factor  in  this  particular  case  was  the  trauma. 
Gastric  ulcers,  if  not  relieved  surgically  or 
by  dietetic  means,  degenerate,  and  in  this 
degeneration  assume  malignant  characteris- 
tics; hence,  the  pre-cancerous  lesion  that  can 
be  definitely  associated  with  the  development 


STOMACH  83 

of  a  malignancy  is  a  gastric  ulcer.  (See  chap- 
ter on  Precancerous  Lesions.) 

The  most  frequent  sites  of  gastric  malig- 
nancies are  the  lesser  curvature,  the  cardia, 
and  the  pylorus.  It  may  be  interesting  to 
note  that  gastric  ulcer  also  develops  in  these 
areas.  Inasmuch  as  the  only  satisfactory  re- 
lief of  neoplasm  of  the  stomach  is  surgical 
procedure,  it  is  very  essential  to  locate  the 
position  of  the  growth.  In  general,  a  malig- 
nancy of  the  stomach,  no  matter  where  its 
location,  will  be  observed  to  have  the  same 
effect  upon  the  composition  of  the  blood  and 
urine  as  malignancy  in  other  areas.  In  con- 
nection with  sulphur  metabolism  in  carci- 
nomatous conditions,  it  is  interesting  to  note 
that  several  years  ago  Schmidt  of  Vienna 
adopted  as  a  differential  sign  the  failure  of 
sulpho-cyanate  reaction  in  the  saliva.  How- 
ever, too  much  stress  cannot  be  placed  upon 
this  qualitative  test.  A  more  certain  diag- 
nosis can  be  arrived  at  from  a  knowledge  of 
the  gastric  contents. 

Differential  Diagnosis. — Inasmuch  as  gas- 
tric ulcer  may  be  considered  a  pre-cancerous 
lesion,  it  is  important  in  this  connection  to 
consider  means  of  detecting  an  ulcerating 
process  in  the  gastric  mucosa.     An  ulcer  of 


84  CANCER 

the  chlorotic  type  is  of  a  hematogenous 
origin;  /.  e.^  it  is  subsequent  to  circulatory 
changes,  it  has  primarily  a  low  hemoglobin 
index  and  a  low  red  cell  count. 

The  chlorotic  type  of  ulcer  is  more  com- 
monly found  in  young  girls  than  in  other 
classes  of  patients.  Ulcers  of  this  type  leave 
no  after-effects,  and  no  observations  have  been 
made  of  the  degeneration  of  such  an  ulcer 
into  a  malignancy.  An  ulcer,  however,  of  a 
mechanical  origin  or  subsequent  to  a  syphilitic 
or  a  tuberculous  infection  is  to  be  considered 
liable  to  degeneration.  Ulcers  of  this  type 
are  characterized  by  stasis  of  food  in  the 
stomach,  a  hyperacidity  of  the  contents,  and 
an  occasional  trace  of  blood  (all  types  except 
chlorotic).  The  pain  commonly  called  epi- 
gastric is  referred  to  the  epigastrium  and  may 
radiate  upwards  and  to  the  back.  A  large 
number  of  cases  of  ulcers  that  have  shown 
recurrence  have  been  studied  for  disturbance 
in  sulphur  and  nitrogen  metabolism,  and  it 
has  been  found  that  they  produce  no  effect 
upon  the  concentration  of  the  non-protein 
nitrogen  and  sulphur  of  the  blood  and  urine, 
until  they  become  malignant. 

The  degeneration  of  these  ulcers  into  neo- 
plasms is  always  of  the  carcinomatous  and  not 


STOMACH  85 

of  the  sarcomatous  type.  Such  a  degenera- 
tion can  be  detected  first  by  a  gradual  de- 
crease in  the  hyperacidity  of  the  gastric 
contents,  and  secondly  when  the  neoplasm  has 
become  definitely  established  by  the  propor- 
tionate increase  in  the  neutral  sulphur  of  the 
urine.  Inasmuch  as  this  degeneration  may 
take  place  unaccompanied  by  pain,  and  there- 
fore without  the  patient's  knowledge  of  his 
condition,  we  would  recommend  the  study  of 
the  composition  of  the  urine  and  gastric  con- 
tents for  some  period  of  time  following  the 
disappearance  of  pain  or  the  relief  of  an 
ulcerative  condition.  In  a  volume  of  this 
type  naturally  we  cannot  dwell  too  long  on 
every  minute  symptom  associated  with  these 
conditions,  but  on  account  of  the  increasing 
frequency  with  which  cancer  of  the  stomach 
is  commencing  to  be  found,  we  think  it  ad- 
visable to  speak  more  fully  than  on  some 
other  conditions  mentioned. 

Gastric  carcinoma  may  be  differentiated 
from  an  anacid  gastritis  by  the  composition 
of  the  gastric  contents  or  by  the  sulphur  par- 
tition of  the  urine.  Anacid  gastritis,  like  car- 
cinoma, is  characterized  by  a  low  acidity  of 
the  gastric  contents.  In  this  condition,  how- 
ever,   we    do    not    find    blood   by   chemical 


86  CANCER 

methods,  nor  do  we  find  lactic  acid  or  the 
Boas-Oppler  bacillus.  Gastritis  produces  no 
changes  in  the  body  fluids,  as  the  blood  or 
urine,  and  this  fact  is  of  vast  importance  in 
dififerential  diagnosis. 

Neoplasms  of  the  Pancreas. — The  pancreas 
is  intimately  associated  with  carbohydrate 
metabolism.  In  this  connection  its  chief  func- 
tion consists  in  the  removal  of  diastase  or 
starch-splitting  enzymes  from  the  blood  and 
the  secretion  of  these  enzymes  in  the  duode- 
num. A  malignancy  at  the  head  of  the  pan- 
creas will  inhibit  the  activity  of  the  cells,  and 
therefore  a  failure  to  eliminate  diastase  from 
the  blood  into  the  duodenum  will  follow.  This 
can  be  detected  by  an  increase  of  the  activity  of 
the  diastase  in  the  blood  and  a  decreasing  ac- 
tivity in  the  duodenal  juice ;  for  the  calculation 
of  these  enzyme  activities,  the  procedures  we 
have  found  most  available  are  the  methods 
for  the  diastatic  activity  of  the  blood  and 
duodenal  juice  as  described  by  Killian  and 
Myers.  The  activity  in  the  blood  in  these 
conditions  will  rise  to  twice  the  normal,  with 
a  consequent  hyperglycemia.  A  failure  to 
produce  lipase  of  the  pancreas  will  be  indi- 
cated by  an  abnormal  quantity  of  neutral  fat 
in  the  feces.    A  neoplasm  of  the  neck  of  the 


STOMACH  87 

pancreas  may  by  mechanical  pressure  upon 
its  duct  restrict  the  passage  of  the  pancreatic 
juice  into  the  duodenum.  In  these  cases 
effects  similar  to  those  noted  above  will  be 
observed.  By  the  methods  at  our  disposal  it 
would  be  impossible  to  localize  the  neoplasm 
to  either  the  head  or  the  neck  of  the  pancreas. 
However,  such  a  differentiation  is  of  no  great 
value,  inasmuch  as  surgical  interference  is  in- 
dicated in  either  condition.  A  gumma  or 
tuberculous  process  inhibiting  the  activities  of 
the  pancreas  may  be  differentiated  from  a 
carcinomatous  growth  by  the  fact  that  no  con- 
ditions other  than  carcinomatous  disturb  the 
concentrations  of  the  sulphur  components  of 
the  urine. 

Intestinal  Tract. — For  diagnosis  of  neo- 
plasm of  the  intestinal  tract  we  may  depend 
to  a  limited  degree  upon  the  presence  of 
pathological  constituents  in  the  feces.  If  the 
process  is  obstructional,  chronic  constipation 
will  be  the  result.  This  constipation,  how- 
ever, may  be  relieved  by  enemas  or  cathartics. 
It  will  be  found  that  the  feces,  principally 
those  following  enemas  or  cathartics,  contain 
occult  blood.  The  presence  of  blood  cannot 
be  indicated  microscopically  unless  the  neo- 
plasm is  in  the   rectum  or  sigmoid  flexure. 


88  CANCER 

For  the  detection  of  blood  from  a  neoplasm 
higher  up  in  the  intestinal  tract,  we  must  de- 
pend on  chemical  means.  The  feces  will  be 
found  also  to  contain  considerable  quantities 
of  mucus  and  necrotic  epithelial  cells.  It  is 
in  the  localization  of  tumors  of  the  small  or 
large  intestine  that  the  X-ray  is  of  the  greatest 
value,  and  for  the  diagnosis  of  tumors  of  this 
region  we  must  depend  more  upon  the  X-ray 
findings  and  the  general  effect  of  the  growth 
upon  the  physical  condition  of  the  patient  and 
the  composition  of  the  urine  and  the  blood, 
rather  than  upon  the  composition  of  the  feces. 
The  sulphur  partition  in  these  cases  is  of 
value. 

A  very  common  affection  which  shows 
tendencies  toward  malignant  formation  is 
"Smoker's  Patch,"  or  leucoplakia  of  the 
tongue.  It  appears  as  a  small  circumscribed 
white  patch  upon  the  tip  or  margin  of  the 
tongue  and  is  most  commonly  seen  in  exces- 
sive smokers  or  in  individuals  giving  a  syph- 
ilitic history.  In  smokers  its  origin  is  most 
probably  due  to  the  irritating  action  of  ob- 
noxious gases  upon  the  epithelium  of  the 
tongue.  If  untreated  it  develops  malignant 
characteristics  that  form  metastases  in  the 
walls  of  the  pharynx.     The  only  satisfactory 


STOMACH  89 

procedure  for  the  relief  of  this  condition  is 
the  complete  destruction  with  the  cautery.  In 
the  development  of  neoplasm  from  leuco- 
plakia  or  other  pre-cancerous  conditions  we 
must  recognize  a  predisposing  cause,  and 
whether  the  exciting  cause  be  bacillary  infec- 
tion, trauma,  or  chronic  inflammation,  we 
cannot  say.  However,  the  pathologist  cannot 
too  strongly  urge  upon  the  surgeon  the  neces- 
sity of  a  complete  destruction  of  a  leucoplakia 
as  a  predisposing  lesion  of  carcinomatous  de- 
velopment. 

{Note, — The    normal    amount   of    neutral 
sulpho-cyanate  has  never  been  determined.) 


CHAPTER   IV 

Differential  Diagnosis  between  Epithe- 
lioma, Syphilis,  and  Diseases  of  the 
Skin 

In  a  work  of  this  character  it  hardly  seems 
advisable  to  devote  a  great  deal  of  space  to 
dwelling  on  the  somewhat  minor  points  of 
difference  between  epithelioma  in  its  various 
forms  and  syphilis  and  certain  diseases  of  the 
skin.  Although  those  experienced  know  that 
again  and  again  mistakes  in  diagnosis  occur 
often,  many  an  individual  has  been,  and  is 
being,  operated  on  for  cancer  who  is  really 
suffering  from  some  of  the  protean  forms  of 
syphilis.  In  our  experience  (based  to  a  con- 
siderable extent  upon  observations  made  in 
homes  for  incurables)  we  find  syphilis  mis- 
taken for  carcinoma  a  hundred  times  more 
frequently  than  we  find  carcinoma  mistaken 
for  syphilis. 

As  stated  above,  it  seems  to  us  more  fitting 
to  devote  space  to  a  general  consideration  of 
the  means  at  our  disposal  for  making  positive 
what  diseases  exist,  than  to  dwell  much  on  all 

90 


DIFFERENTIAL  DIAGNOSIS  9 1 

the  clinical  points  that  may  present  themselves 
to  the  eye  alone.  These  latter  are  more  care- 
fully considered  in  some  of  the  works  on  Dis- 
eases of  the  Skin,  and  are  often  graphically 
portrayed  by  means  of  color  plates.  The 
Wassermann  reaction  is  not  always  a  safe 
guide,  because  it  is  very  often  absent  in  old 
syphilitic  cases.  When  found  to  be  present, 
its  diagnostic  value  naturally  has  great  weight. 
In  many  cases,  particularly  those  of  suspected 
gumma,  it  is  necessary  to  try  very  thoroughly, 
for  at  least  a  month,  an  intensive  anti-syph- 
ilitic treatment  and  to  observe  its  effects  be- 
fore the  diagnosis  between  it  and  epithelioma 
can  be  clearly  made  out.  It  is  probably  wiser 
in  such  cases  to  resort  at  first  to  mercury  in 
some  form  and  the  iodides,  for  this  purpose, 
than  to  salvarsan.  It  may  be  well  to  note 
here  some  clinical  observations  which  we  have 
made.  These  observations  are  not  particu- 
larly new,  but  it  has  been  surprising  to  notice 
in  how  many  cases  proper  precautions  have 
not  been  taken  to  clear  up  doubts  which  might 
exist  as  to  the  nature  of  a  lesion  being  syph- 
ilitic or  carcinomatous,  through  the  careful 
carrying  out  of  simple  therapeutic  tests. 
Iodide  of  potash,  the  administration  of  which 
it  is  well  known  has  such  an  effect  in  causing 


92  CANCER 

the  diminution  of  a  syphilitic  gumma  when 
the  system  is  thoroughly  saturated  with  it, 
should  be  administered  on  an  empty  stomach, 
instead  of  after  meals,  as  is  so  often  done, 
when  it  has  a  tendency  to  form  the  iodide 
of  starch. 

Mistakes  often  occur  in  large  hospitals  in 
the  proper  and  systematic  medication  of  pa- 
tients, often  so  extremely  important  as  an  aid 
to  diagnosis  in  the  above-mentioned  condi- 
tions, unless  great  care  is  exercised  on  the  part 
of  the  house  staff  and  attending  physicians. 

Mixed  treatment,  containing  iodide  of  pot- 
ash as  it  does,  should  also  be  administered 
when  the  stomach  is  empty;  and  a  very  thor- 
ough course  of  mercury  and  the  iodides,  of 
months'  duration,  should  be  instituted,  and 
the  effect  carefully  watched  (both  constitu- 
tional and  local)  in  all  doubtful  cases.  When, 
after  this  therapeutic  test,  no  change  has  been 
observed  in  the  appearance  of  a  doubtful 
lesion,  the  results  of  this  test  should  not  be 
considered  infallible,  but  should  be  followed 
by  the  administration,  at  least  twice,  of  old 
salvarsan  when  possible  to  obtain  it.  We 
have  found  "Smoker's  Patch,"  when  due  to 
syphilis,  and  gumma  of  the  corpora  caver- 
nosa, to  be  the  most  difficult  conditions  to  yield 


DIFFERENTIAL  DIAGNOSIS  93 

to  anti-syphilitic  treatment,  and  thereby  in  a 
doubtful  case  enable  us  to  establish  a  definite 
diagnosis. 

It  hardly  seems  necessary  to  remark  that 
in  doubtful  lesions  too  much  reliance  should 
not  be  placed  upon  the  results  of  a  history  of 
therapeutic  tests  previously  given  by  the  in- 
dividual having  such  lesions.  The  effect  of 
hypodermic  mercurial  medications  has  not  the 
same  diagnostic  value  as  the  procedures  men- 
tioned above. 

Seborrhcea  and  epithelioma  may  sometimes 
be  easily  mistaken.  It  should  be  remembered 
that  almost  all  forms  of  cancer  of  the  skin 
commence  with  lentil-shaped  papules  under 
the  skin  before  the  breaking  down  of  the  tis- 
sue occurs.  Chancre,  herpes,  eczema,  and 
innocent  erosions  may  be  mistaken  for  epi- 
thelioma. It  should  also  be  borne  in  mind 
that  while  an  epithelioma  may  develop 
through  the  breaking  down  of  near-by  mul- 
tiple islets,  syphilitic  growths  have  a  tendency 
to  be  more  multiple.  This  character,  too, 
tends  to  distinguish  it  from  eczema,  occasion- 
ally there  being  some  resemblance  between  the 
two,  particularly  when  they  occur  on  the  face. 
The  border  of  epithelioma  is  more  sharply 
defined,  and  there  is  less  infiltration.     The 


94  CANCER 

diagnosis  of  lupus  can  be  helped  by  the  his- 
tory, the  age  of  the  patient,  and  the  tendency 
toward  multiplication  in  lupus,  together  with 
the  slow  growth  of  the  latter,  and  the  fact  that 
it  has  no  tendency  to  cause  constitutional  im- 
pairment. Condylomatous  warts  and  allied 
conditions  may  sometimes  simulate  epitheli- 
oma, and  to  distinguish  them  from  these,  and 
any  of  the  conditions  mentioned  above  which 
may  simulate  them,  when  practical,  a  speci- 
men should  be  obtained,  and  the  results  of  the 
microscopical  examination  by  a  good  pathol- 
ogist noted. 

The  value  of  obtaining  a  careful  history 
we  wish  to  call  attention  to  again,  particu- 
larly as  regards  the  question  of  heredity, 
which  is  often  overlooked.  It  is  referred  to 
again  in  this  work;  the  value  of  the  sulphur 
findings  in  the  blood  and  the  urine  are  also 
referred  to,  as  is  the  benefit  to  be  obtained 
from  skilful  examination  by  X-ray  pictures. 
The  use  of  some  or  all  of  these  latter  methods 
helps  wonderfully  in  doubtful  cases,  both  in 
the  diagnosis  as  well  as  in  the  prognosis,  and 
in  furnishing  indications  for  treatment.  Some 
of  the  above  methods  are  just  coming  into 
general  use,  and  one  or  two  of  them  have 
practically  never  been  tried  before. 


CHAPTER   V 

Diagnosis  by  X-Ray  and  Cystoscope 

Now  that  examination  plates  by  the  Roent- 
gen ray  are  being  made  more  and  more  fre- 
quently, as  they  should  be — not  only  as  a 
diagnostic  measure  to  show  conditions  affect- 
ing the  bones,  but  as  an  aid  in  diagnosing  any 
diseases  of  the  heart,  lungs,  pleura,  abdominal 
organs,  and  urinary  system — their  use  has  not 
only  been  of  great  aid  in  the  diagnosis  of  any 
given  case,  but  is  tending  to  alter  to  a  great 
degree  our  conception  of  the  nature  of  the 
disease.  This  is  true  of  malignant  diseases 
more  than  any  other.  The  surgeon  is  no 
longer  in  the  position  concerning  such  opera- 
tions as,  e.  g.^  cancer  of  the  breast,  that  he  was 
only  a  very  few  years  ago  before  the  exami- 
nation of  the  chest  by  the  Roentgen  ray  be- 
came such  a  matter  of  routine.  Naturally  the 
conditions  shown  in  the  plates,  such  as  the 
presence  or  absence  of  enlargement  of  the 
glands  at  the  base  of  the  lungs,  single  or  mul- 
tiple,   indications  of   tumors   in   the  pleura, 

95 


96  CANCER 

mediastinum  or  esophagus,  probably  above 
all,  peri-bronchial  thickening,  together  with 
other  diagnostic  evidence,  among  which  may 
be  mentioned  the  amount  of  unoxidized  sul- 
phur in  the  urine,  have  in  a  given  case  an 
effect  in  modifying  the  decision  as  to  whether 
an  operation  is  to  be  performed  or  not,  also 
the  character,  and  above  all  the  prognosis  in 
any  surgical  measure  undertaken.  In  the  in- 
terpretation of  any  plates  it  is  hardly  neces- 
sary to  insist  that  the  most  careful  considera- 
tion must  be  given  to  the  proper  interpretation 
of  the  shadows,  and  the  testimony  furnished 
through  their  use  should  be  considered  only 
in  connection  with  the  testimony  furnished  by 
other  diagnostic  factors  in  any  given  case. 
Naturally  the  co-operation  of  the  attending 
surgeon  and  the  radiographer  is  most  impor- 
tant. This  is  particularly  true  in  plates  in 
which  the  shadows  are  as  distinct  as  those  of 
the  bones,  for,  aside  from  trauma,  so  many 
other  conditions  may  affect  the  bones,  either 
the  periosteum,  the  surface,  or  their  centers, 
that  mistakes  may  very  easily  occur.  In  our 
own  work  we  have  found  that  the  appearance 
of  dead  bone  shown  on  a  plate,  without  other 
factors  to  account  for  its  presence,  is  very  in- 
dicative of  being  secondary  to  some  constitu- 


X-RAY  AND  CYSTOSCOPE  97 

tional  disease,  of  which  the  primary  focus  or 
foci  is  in  some  other  organ  of  the  body,  and 
which  it  is  often  extremely  difficult  to  locate. 
To  illustrate  further,  we  have  noticed  hyper- 
nephroma of  the  kidney  so  small  as  not  to 
cause  enlargement  of  that  organ,  cause 
necrosis  in  the  pelvic  bones  and  sternum, 
without  giving  rise  to  indications  of  kidney 
disturbance. 

Syphilitic  and  malignant  diseases  of  the 
bone  are  often  difficult  to  diagnosticate  from 
one  another.  Generally  speaking,  syphilitic 
growths  of  the  bone  are  apt  to  be  smaller, 
more  nodular  and  numerous  than  malignant 
growths.  Malignant  growths  of  the  bone  are 
more  apt  to  be  secondary  to  a  primary  focus 
in  some  other  portion  of  the  body.  Sarcoma 
causes  more  of  an  expansion  of  the  bone  than 
cancer.  The  age  of  the  patient  and  other  fac- 
tors often  aid  in  the  diagnosis.  Sarcoma  oc- 
curs more  often  in  the  periosteum  or  endos- 
teum  than  cancer.  In  the  lung,  primary  can- 
cerous growths  are  rare.  The  shadows  given 
by  them  are  not  always  clear;  they  may  be 
taken  for  aneurism.  They  are,  however,  oc- 
casionally met  with  both  in  the  lobes  and  in 
the  hilus.  Those  in  the  lobes  generally  give 
a  shadow  fairly  clear,  with  a  line  of  demar- 


98  CANCER 

cation.  They  can  be  differentiated  from 
pneumonia  by  the  clinical  history.  They  give 
a  more  definite  outline  than  tuberculosis,  and 
there  is  less  apt  to  be  evidence  of  involvement 
of  the  lung.  When  they  occur  in  the  hilus 
they  are  apt  to  confine  themselves  also  to  a 
lobe.  Secondary  cancers  are  found  in  a 
nodular  form,  and  a  diffuse  form  as  well. 
Neoplastic  nodules  can  be  easily  made  out 
by  the  plates  and  differentiated  from  tuber- 
culosis, as  they  give  no  evidence  by  the 
stethoscope,  and  are  quite  characteristic.  In 
diffuse  form  they  are  apt  to  occur  at  the  bot- 
tom of  the  lung,  and  either  cause  an  extension 
into  the  pleura  or,  on  a  plate,  present  an 
appearance  of  an  epanchement  pleuritique. 
If  confined  to  the  lung  alone,  these  diffused 
secondary  growths  generally  give  no  symp- 
toms on  auscultation,  if  the  pleura  is  not  in- 
volved; but  very  often  these  cases  are  mixed 
up  with  a  true  involvement  of  the  pleura. 

One  factor  also  to  be  considered  here  is  the 
negative  value  of  these  plates  when  the  pic- 
tures are  carefully  taken  by  a  competent 
radiographer.  The  mediastinum  is  clear,  the 
pleura  casts  no  shadows,  and  no  nodules  can 
be  made  out  around  the  bronchi,  which  is 
good  evidence  that  metastases  have  not  as  yet 


X-RAY  AND  CYSTOSCOPE  99 

taken  place.  It  should  be  noted  that  these 
nodules  are  small,  and  when  the  mediastinum 
is  affected  it  is  difficult  to  have  the  discern- 
ible shadows  appear.  The  small  nodules 
around  the  bronchi  are  easier  to  be  made  out, 
as  is  also  the  thickening  of  the  pleura,  which 
casts  a  denser  shadow  than  when  due  to  sim- 
ple pleuritic  effusion  of  liquid,  although  it 
should  be  remembered  that  the  cancerous  in- 
vasion of  the  pleura  in  itself  may  give  rise 
to  association  with  effusion. 

Malignant  growths  of  the  esophagus,  if  of 
any  size,  after  the  administration  of  bismuth, 
are  shown  clearly  on  a  plate.  Radiography 
of  the  esophagus  is  too  often  overlooked,  and 
malignant  growths  are  frequently  not  diag- 
nosed by  this  measure  until  they  have  existed 
for  a  considerable  time  and  become  of  quite 
a  large  size. 

It  is  rather  beyond  the  plan  of  this  volume 
to  give  more  than  a  general  outline  of  the 
technique  necessary  to  bring  out  all  the  diag- 
nostic points  that  may  be  found  in  connection 
with  the  examinations  of  the  stomach  by 
radiography;  reference  is  made  to  the  last 
edition  of  Knox's  "Radiography,  X-Ray 
Therapeutics  and  Radium  Therapy,"  pub- 
lished by  Macmillan,  as  to  the  details  of  such 


lOO  CANCER 

procedures  as  the  administration  of  the  opaque 
meal,  bismuth,  the  position  of  the  patient  for 
examination,  and  interpretation  of  the  shad- 
ows found.  He  states,  quoting  Holzknecht, 
that  a  simple  ulcer  of  the  stomach  is  rarely 
seen,  although  it  may  be  suspected  from  the 
absence  of  shadows,  indicating  the  passage  of 
food  through  the  pylorus.  In  malignant  dis- 
ease involving  the  lesser  curvature  and  spread- 
ing through  the  pylorus,  the  latter  point  is 
more  or  less  fixed  and  held  higher  up  than 
usual;  food  may  be  seen  passing  through  the 
stricture;  a  sharp  and  persistent  angle  or 
irregularity  in  the  pyloric  region  is  generally 
indicative  of  malignant  stricture;  finally,  a 
shadow  of  the  growth  may  at  times  be  seen 
on  the  radiographs. 

Malignant  diseases  may  occur  anywhere  in 
the  stomach.  It  sometimes  shows  on  the  plate 
by  giving  a  ragged  or  irregular  shadow,  ir- 
regularity being  due  to  the  projection  of  the 
growth  into  the  bismuth  food;  generally  also 
a  characteristic  picture  of  stasis  is  presented. 
The  abnormal  conditions  of  both  the  small 
and  large  intestines  following  the  bismuth 
meal  can  either  be  differentiated  by,  or  else 
valuable  testimony  obtained  from,  the  X-ray 
examinations.     Most  abnormal  conditions  of 


X-RAY  AND  CYSTOSCOPE  lOI 

the  intestines  present  a  picture  of  stasis,  to  a 
more  or  less  marked  degree.  Kinks  may  be 
occasionally  made  out  by  this  measure,  and  as 
regards  the  duodenum,  sometimes  an  ulcer,  if 
deep,  can  be  differentiated. 

Examination  of  the  urinary  tract  may  be 
performed  by  means  of  the  X-ray  pictures 
alone,  through  the  use  of  the  X-ray  in  con- 
nection with  a  metallic  ureteral  catheter,  or 
following  an  injection  of  some  salts  of  silver 
or  thorium  into  the  pelvis  of  the  kidney,  and 
rarely  by  an  injection  of  some  bismuth  salts 
into  the  bladder. 

Just  here  it  is  only  desired  to  mention  the 
value  of  the  X-ray  for  diagnostic  purposes 
when  used  in  showing  tumors  of  these  organs. 
When  used  alone,  without  the  other  aids  just 
mentioned,  it  is  doubtful  if  a  positive  diag- 
nosis of  tumor  of  the  kidney  can  be  made  by 
the  use  of  the  Roentgen  ray  unaided.  In 
skilful  hands,  however,  a  shadow  can  be  pre- 
sented which  will  demonstrate  if  any  enlarge- 
ment of  the  kidney  exists,  while  the  density  of 
the  shadow  given  may  at  times  aid  in  render- 
ing positive  a  diagnosis  of  tumor. 

Where  examinations  of  the  urinary  tract 
are  to  be  made,  great  care  should  be  used  to 
see  that  the  intestines  are  thoroughly  emptied 


I02  CANCER 

of  their  contents  before  the  picture  is  taken, 
so  that  intestinal  gases  may  not  give  rise  to 
shadows;  and  where  one  kidney  is  examined, 
a  picture  of  the  other  one  should  always  be 
taken. 

The  value  of  the  cystoscope  as  a  method  of 
diagnosing  malignant  growth  is  naturally 
confined  to  those  growths  occurring  in  or 
associated  with  the  bladder.  Through  the 
use  of  the  cystoscope,  where  it  is  suspected 
that  a  malignant  growth  of  the  kidney  exists, 
not  infrequently  the  ureteral  catheter  can  be 
passed  through  the  ureter  to  the  kidney,  and 
through  that  enough  solution  of  thorium,  col- 
largol,  or  argyrol  introduced,  and  an  X-ray 
picture  taken.  The  plate  will  show  the  shape 
of  the  pelvis  and  the  kidney,  and  in  that  way 
may,  in  connection  with  other  indications, 
give  a  fairly  correct  view  as  to  whether  a  tu- 
mor of  the  kidney  exists  or  not.  The  inability 
to  pass  the  ureteral  catheter  in  skilled  hands 
indicates  the  closing  of  the  ureter,  and  if  a 
waxed  tip  ureteral  bougie,  or  some  other  form 
of  metal  ureteral  bougie,  fails  to  indicate  the 
presence  of  stone,  testimony  is  furnished  that 
tends  to  strengthen  the  diagnosis  of  some  form 
of  tumor.  Very  frequently,  where  a  suspected 
growth  exists  in  the  kidney  or  ureter,  it  is 


X-RAY  AND  CYSTOSCOPE  1 03 

better  to  do  an  exploratory  operation  than  to 
run  the  risk  of  misleading  diagnosis  or  of 
irritation  of  the  pelvis  of  the  kidney  through 
the  passage  of  the  ureteral  catheter.  Con- 
cerning this  subject,  reference  is  made  to 
Greene  and  Brooks'  ^'Urinary  Disease  and 
Diseases  of  the  Kidney,"  4th  edition  (W.  B. 
Saunders  Co.,  1917),  or  to  Braasch's  ^'Pyelog- 
raphy" (W.  B.  Saunders,  1917). 

It  is  in  the  bladder,  very  naturally,  that 
the  cystoscope  is  of  such  value  in  demonstrat- 
ing a  growth.  Unfortunately,  many  of  these 
tumors  of  the  bladder  are  associated  v^ith  a 
large  prostate,  so  that  the  cystoscope  cannot 
be  passed.  When  it  can  be,  an  exploring 
cystoscope  in  the  hands  of  any  one  that  is 
skilled  in  its  manipulation  will,  under  ordi- 
nary circumstances,  give  a  fairly  clear  picture 
of  any  abnormal  lesion  on  the  bladder  walls. 

Just  here,  however,  it  is  necessary  once 
more  to  return  to  the  consideration  of  the  re- 
semblance between  various  forms  of  syph- 
ilitic tumors,  or  ulcerations  of  the  bladder, 
and  other  ulcerations  or  growths,  either  ma- 
lignant or  benign.  Syphilis  of  the  bladder 
was  never  recognized  as  a  definite  entity  until 
the  cystoscope  came  into  common  use.  Some 
of  us  had  recognized  and  written  about  syph- 


I04  CANCER 

ilis  as  affecting  the  bladder,  particularly  as 
a  cause  of  contracted  bladder,  from  clinical 
observation  alone.  (See  reference  in  earlier 
editions  of  Greene  and  Brooks,  ut  supra.) 
But  even  now  these  conditions  are  being 
classified,  and  very  little  has  been  written 
concerning  them  in  English.  Syphilis  attacks 
the  bladder,  somewhat  generally  speaking,  in 
three  different  forms.  In  its  earlier  stages  it 
attacks  the  bladder,  causing  numerous  small 
ulcerations,  somewhat  resembling  those  of 
mucous  patches  on  the  tongue  and  mouth.  In 
the  later  stages  the  ulcerations  are  smaller  in 
number,  but  are  apt  to  be  deeper  and  of  a 
polycystic  character;  and  in  its  still  later 
stage  it  gives  rise  to  gumma  of  the  bladder. 
These  gummata  of  the  bladder  have  a  charac- 
teristic appearance,  and,  having  once  been 
seen,  are  more  easily  recognized  than  de- 
scribed. They  are  very  well  illustrated  in  the 
colored  plates  of  an  article  by  G.  Gayet  and 
E.  Favre,  Journal  de  Neurologic^  July,  1914, 
and  have  been  redrawn  in  black  and  white 
and  published  in  the  4th  edition  of  Greene 
and  Brooks  {ut  supra).  They  sometimes,  in 
a  rough  way,  resemble  a  bunch  of  grapes, 
also  sessile  tumors  or  pediculated  tumors,  be- 
ing papillomatous  in  shape.    The  later  ulcer- 


X-RAY  AND  CYSTOSCOPE  I05 

ations  of  syphilis  of  the  bladder  may  be 
mistaken  for  tuberculosis  of  the  bladder  when 
viewed  under  the  cystoscope,  and  probably 
often  have  been  so  mistaken.  Gummata  of 
the  bladder  undoubtedly  have  been  and  are 
being  mistaken  either  for  malignant  growth 
of  the  bladder  or  for  benign  bladder  papillo- 
mata;  and  in  all  probability,  in  many  of  the 
cases  that  have  been  recorded  as  cures  follow- 
ing operations  for  tumor  of  the  bladder,  these 
tumors  have  been  gummata,  and  neither  ma- 
lignant nor  simple  papillomata.  These  syph- 
ilitic lesions  have  more  of  a  tendency  to  grow 
upward  and  less  of  a  tendency  to  infiltrate  the 
bladder  wall  than  malignant  growths.  From 
either  malignant  growths  or  from  benign 
papillomata  they  are  at  times  extremely  diffi- 
cult to  differentiate,  and  when  possible  a  care- 
ful microscopical  examination  of  any  bladder 
growths  should  be  made.  Probably  where  a 
syphilitic  ulceration  of  the  bladder  has  been 
marked,  its  after-effect  is  to  cause  connective 
tissue  in  the  bladder  wall  and  give  rise  to 
contracted  bladder.  It  may  also  be  stated 
that  many  cases  of  late  syphilis  of  the  nervous 
system,  such  as  locomotor  ataxia,  have  syph- 
ilis of  the  bladder  as  well,  instead  of  having 
their  bladder  symptoms  entirely  due  to  some 


I06  CANCER 

sclerotic  or  other  condition  in  the  spinal  cord; 
syphilis  of  the  bladder  may  coexist  with  them. 
In  these  cases  mild  anti-syphilitic  treatment 
is  of  benefit  for  the  bladder  symptoms,  in 
addition  to  whatever  local  treatment  may  be 
given  them.  In  all  doubtful  cases  of  bladder 
lesion  portrayed  by  the  cystoscope,  all  other 
diagnostic  factors  possible  to  obtain  should 
be  collected  and  analyzed  before  a  diag- 
nosis of  the  presence  or  absence  of  malignant 
growth  of  the  bladder  is  made. 


CHAPTER   VI 

General  Consideration  of  the  Condition 
OF  Blood,  Hair,  Nails,  and  Saliva 

In  addition  to  what  has  previously  been 
mentioned  in  this  volume  concerning  the  vari- 
ous methods  to  be  considered  in  the  diagnosis 
of  malignant  growths,  there  are  a  few  others 
which  we  believe  will,  in  the  not  far-distant 
future,  be  taken  into  account  as  diagnostic 
factors,  and  concerning  which  at  the  present 
time  comparatively  little  is  known  or  has 
been  written.  They  are  of  enough  importance 
at  least  to  be  mentioned. 

Concerning  the  blood  in  general,  as  regards 
its  chemical  analysis,  there  is  still  a  great  deal 
of  work  to  be  done  to  establish  definitely  the 
amount  of  the  chemical  constituents  in  nor- 
mal blood,  and  also  in  the  discovery  of  new 
tests  which  will  demonstrate  the  amount  pres- 
ent of  some  of  its  constituents,  where  only 
small  quantities  of  blood  can  be  obtained  for 
examination. 

The  work  done  by  us  apparently  demon- 
107 


Io8  CANCER 

strates  what  the  normal  amount  of  sulphur 
is  in  the  blood,  about  36  milligrams  to  100 
c.c.  of  blood.  But  still  further  work  needs 
to  be  done  to  demonstrate  the  absolute  cor- 
rectness of  these  figures,  that  is,  as  to  whether 
this  increase  of  sulphur  in  the  blood  is  found 
in  carcinoma  alone  or  not,  as  our  work  would 
seem  to  show,  and  further  work  in  the  chem- 
istry of  the  blood  is  needed  to  demonstrate 
the  normal  amount  of  potash  and  some  other 
substances.  It  would  appear  that,  within  the 
next  few  years,  judging  from  the  rapid  ad- 
vance made  recently  in  discovering  new  meth- 
ods for  estimating  the  chemical  constituents  of 
the  blood,  the  chemist  will  be  more  and  more 
frequently  called  on  to  examine  the  chemical 
blood  constituents  in  given  cases.  It  would 
also  appear  that  these  examinations  will  be 
made  with  increasing  ease  and  be  of  more  and 
more  frequent  aid  in  the  diagnosis  of  many 
diseased  conditions.  In  addition  to  the  infor- 
mation that  can  be  obtained  from  the  blood 
at  the  present  time,  and  what  may  be  expected 
from  its  chemical  analysis  in  the  near  future, 
there  are  other  factors,  such  as  the  observa- 
tion of  the  hair,  condition  of  the  nails,  and 
chemical  examination  of  the  saliva,  which 
may   render   at  times  valuable   information. 


BLOOD,   HAIR,  NAILS,   ETC.  109 

We  are  indebted  to  the  observations  of  an 
ardent  believer  and  scientific  worker  on  the 
subject  of  sulphur  changes  in  the  urine  and 
sulphur  metabolism  in  the  system  in  cancer 
generally,  Dr.  F.  von  Oefele,  for  the  obser- 
vation that  ^^Bald-headed  men  never  have 
cancer^''  ('^Quantitative  Urine  Analysis,  with 
Special  Reference  to  Carcinoma  Metabol- 
ism," Trans.  Ger,  Med.  Soc.^  March  4,  1912). 
Naturally  this  statement  can  only  be  taken 
semi-seriously,  for  the  loss  of  hair  from  the 
scalp  can  be  due  to  many  different  causes. 
But  in  a  general  way  there  is  probably  some 
truth  in  the  statement,  for  it  seems  to  be  true 
that  sulphur  plays  a  very  important  part  in 
the  development  of  the  hair,  and  that  the  lack 
of  sulphur  also  plays  a  part  in  causing  its  loss. 
Sulphur  changes  are,  possibly,  the  cause  of 
the  falling  out  of  the  hair  after  an  acute  in- 
fectious disease  like  typhoid.  Sulphur  which 
would  naturally  tend  to  nourish  the  hair  and 
the  scalp  is  used  up  in  the  intestinal  canal 
in  overcoming  the  products  of  decomposi- 
tion caused  by  the  activity  of  the  infected 
condition  appearing  there.  With  the  increase 
of  sulphur  in  the  system,  such  as  appears  to 
exist  in  individuals  with  malignant  growths, 
it  might  be  expected  that  the  hair  would  re- 


no  CANCER 

ceive  its  proper  amount  of  nourishment  as 
far  as  sulphur  is  concerned;  and,  the  other 
factors  being  normal,  bald-headed  people 
would  be  less  subject  to  malignant  growths, 
so  far  as  the  lack  of  hair  is  an  indication  of 
a  lack  of  an  increase  of  sulphur  in  the  system. 

The  condition  of  the  nails  may  not,  and 
probably  do  not,  demonstrate  anything  of 
diagnostic  value  of  a  malignant  growth.  The 
probabilities  are  that  the  sulphur  element  in 
the  development  of  the  nails  is  comparatively 
a  minor  factor.  Split  nails  may  show  a  lack 
of  potash,  which  is  supposed  to  be  increased 
in  the  case  in  most  individuals  suffering  from 
malignant  disease,  and  in  that  way  be  an  indi- 
cation that  no  such  diseased  condition  exists. 
So  far  as  our  own  observations  go,  it  is  so 
limited  in  this  respect  as  to  have  but  little 
value.  It  is  only  mentioned,  however,  as  one 
of  the  factors  that  should  be  borne  in  mind, 
observed,  and  recorded  in  history  taking. 

The  saliva^  concerning  the  chemical  analysis 
of  which  comparatively  little  work  has  ever 
been  done,  may,  through  its  examination,  occa- 
sionally furnish  valuable  data.  Sulphur  exists 
in  it  in  the  form  of  sulphur  cyanate.  When 
the  normal  amount  is  finally  ascertained  and 
some  easy  test  devised  to  determine  the  excess 


BLOOD,   HAIR,  NAILS,  ETC.  Ill 

or  diminution,  it  may  furnish  an  easy  method 
not  only  of  aiding  in  the  diagnosis  as  to 
whether  or  not  some  departure  from  ordinary 
tissue  metamorphosis  exists,  but  also  be  a 
guide  in  showing  the  effects  on  such  metamor- 
phosis of  any  remedial  measures  which  may 
be  undertaken. 

These  examinations  should  be  of  impor- 
tant value  in  connection  with  such  conditions 
as  ''Smoker's  Patch,"  the  origin  of  which  is 
sometimes  very  difficult  to  determine. 


PART    IV 
TREATMENT   OF    CANCER 

CHAPTER    I 

Basis  of  All  Successful  Treatment  to  be 
Found  in  Measures  Which  Tend  to 
Increase  Tissue  Metamorphosis 

Success  in  the  treatment  of  cancer,  like  that 
of  many  other  diseases,  will  depend  to  a  great 
extent  on  the  diagnosis ;  on  the  correctness  of 
this,  and  the  recognition  of  cancer  in  its 
earlier  stage,  the  principles  of  treatment  are 
founded.  It  is  more  than  possible,  it  is  prob- 
able, that  through  the  recognition  of  a  pre- 
cancerous state,  if  such  a  term  can  justifiably 
be  used,  the  adoption  of  proper  methods,  both 
hygienic  and  medicinal,  to  increase  tissue 
metamorphosis,  will  often  prevent  the  disease 
from  becoming  constitutional,  prolong  the 
life  of  the  individual,  diminish  suffering,  and 
what  may  be  of  even  greater  importance,  limit 
the  activity  of  the  predilection  to  the  disease 

112 


GENERAL  TREATMENT  II3 

which  may  be  transmitted  to  others.  Individ- 
uals in  whose  family  history  may  be  traced  a 
predilection  for  cancer,  in  whom  the  neutral 
sulphur  constituent  of  the  blood  and  the  urine 
are  found  to  be  above  the  normal,  who  show 
a  tendency  towards  a  slow  repair  following 
injury  or  accident,  and  particularly  those 
whose  mucous  membranes  are  unusually  easily 
subject  to  excoration,  or  such  conditions  as 
relapsing  herpes  from  slight  irritation,  belong 
to  this  class. 

The  above  conditions,  or  similar  ones,  are 
considered  of  sufficient  importance  to  be  re- 
ferred to  more  than  once  in  other  portions  of 
this  book.  Concerning  the  medicinal  treat- 
ment in  general  to  be  adopted,  it  is  difficult 
to  separate  the  preparations  to  be  used  into 
clearly  defined  classes.  Somewhat  generally 
speaking,  it  may  be  stated  that  for  internal 
administration  one  class  consists  of  prepara- 
tions which  can  probably  be  considered  as 
tonics.  And  even  the  action  of  these  is  not 
at  the  present  time  clearly  and  distinctly  un- 
derstood, but  they  probably  act  on  the  hema- 
tin  in  the  blood,  and  through  increasing  the 
hematin  in  the  blood  increase  the  resistant 
power  in  the  cell.  To  this  class  belong  ar- 
senic, iron,  manganese,  and  vanadium.     An- 


114  CANCER 

other  class  of  agents,  such  as  selenium  and 
tellurium,  act  as  diuretics,  as  oxidizers,  or 
else  in  some  way  with  which  we  are  not  en- 
tirely familiar,  enter  into  combination  with 
the  sulphur  in  the  cell  in  such  a  form  as  to 
tend  to  stop  increased  cancer-cell  prolifera- 
tion. If  they  act  as  oxidizers,  it  might  be  sur- 
mised that  the  neutral  sulphur  would  be 
changed  to  sulphates,  and  that  an  increase  in 
the  latter  and  a  diminution  of  the  former 
would  be  found  to  follow  their  administra- 
tion. 

The  third  class  contains  such  constituents 
as  condurango,  echinacea  and  the  like,  whose 
action  has  so  far  been  undetermined,  but  in 
advising  the  use  of  which  our  experience  cor- 
roborates that  of  some  others  as  to  the  bene- 
ficial results  following  their  administration, 
which  is  at  the  present  time  (at  least  to  a  con- 
siderable extent)  empirical. 

The  above  refers  to  preparations  for  inter- 
nal administration.  To  a  considerable  extent 
the  same  preparations  not  infrequently  in  a 
different  chemical  combination  will  be  found 
to  be  useful  for  external  application  for  ul- 
cerations associated  with  malignant  growths, 
but  which  are  not  malignant  growths  them- 
selves.    Reference  is  here  made  to  the  state- 


GENERAL  TREATMENT  I15 

ment  in  one  of  the  earlier  chapters  that  the 
ulceration  is  not  the  disease,  but  is  merely  one 
of  its  manifestations,  and  it  is  also  necessary 
to  keep  the  surrounding  tissue  in  as  aseptic 
a  state  as  possible,  so  as  to  prevent  further  in- 
fection. This  is  in  addition  to  whatever  di- 
rect application  over  ulcerated  surfaces  may 
be  made  of  a  stimulating  nature,  such  as 
radium.  X-ray,  arsenous  acid  paste,  or  any 
other  cauterizing  agencies;  applications  to 
certain  ulcerations  are  also  necessary  to  pre- 
vent the  odor  or  to  relieve  pain.  It  has  been 
found  by  us,  that  for  an  external  application 
that  will  relieve  the  odor,  where  skin  sur- 
faces are  ulcerated,  tend  to  stop  the  spread 
of  the  ulceration  and  relieve  the  pain,  a  modi- 
fication of  Dakin's  solution  is  the  most  use- 
ful, made  according  to  our  formula  given 
later  on,  to  which  has  been  added  a  slight 
amount  of  selenium  or  tellurium.  This,  we 
consider,  is  the  most  useful,  although  the  ab- 
solutely ideal  preparations  for  this  purpose 
have  not  as  yet  been  found,  and  probably  never 
will  be,  as  there  are  too  many  different  op- 
posing factors  to  be  controlled  to  make  any 
one  preparation  fulfil  all  the  indications. 
Ointments  which  contain  vanadium  and 
selenium  in  an  unirritating  base  are  sometimes 


Il6  CANCER 

useful  either  in  protecting  surfaces  adjacent 
to  the  ulcerated  area,  or  through  their  effect 
as  an  inunction  in  administering  selenium  to 
the  system.  There  are  several  preparations 
on  the  market  for  this  purpose,  but  care  should 
be  observed  when  using  them  not  to  let  them 
touch  the  ulcerated  surfaces  directly,  as  they 
cause  irritation.  Concerning  deodorizers,  the 
difficulty  met  with  in  solutions  as  deodorizers 
is,  that  a  true  deodorizer  is  a  difficult  thing 
to  discover.  Chlorine  in  some  form  which 
acts  as  a  disguiser  of  any  unpleasant  odor  is 
good,  but  is  in  almost  all  forms  apt  to  be  irri- 
tating. The  preparation  which  we  present 
further  on,  with  a  definite  statement  as  to 
its  manufacture,  is  the  least  irritating  and 
the  most  useful  that  we  have  so  far  been  able 
to  obtain.  Our  experience  with  some  of  the 
preparations  for  external  use  that  will  relieve 
pain,  such  as  orthoform,  although  recom- 
mended by  many,  has  been  disappointing. 
Aristol,  lead  and  opium  wash,  and  many  un- 
irritating  ointments,  all  have  their  place  ac- 
cording to  the  needed  requirements  of  the 
individuals. 

We  prefer  to  mention  throughout  this 
work  the  substances  which  we  ourselves  have 
found  to  be  the  most  beneficial.    And  at  the 


GENERAL  TREATMENT  II7 

risk  of  repetition  it  may  be  stated  that  the 
Dakin's  solution  made  according  to  the 
method  which  we  give,  and  with  the  addi- 
tion which  we  recommend,  is  not  only  of 
great  aid  from  its  constituents,  but  from  the 
method  of  applying  it  through  the  tubes,  a 
constantly  moist  application  to  the  ulcerated 
surfaces  is  insured. 

Life  in  the  open  air  for  these  poor  sufferers 
is  very  beneficial.  In  this  part  of  the  world 
they  are  always  better  in  summer  than  in  win- 
ter. It  has  never  been  thoroughly  tried  out 
so  far  as  we  are  aware,  but  it  would  not  be 
surprising  if  in  days  to  come  it  was  found  that 
life  in  the  open  air  would  be  of  almost  as 
much  benefit  to  individuals  suffering  from 
cancer  where  the  diagnosis  has  been  made  of 
its  existence  in  the  earlier  stages^  as  previously 
referred  to,  as  it  is  in  cases  of  tuberculosis. 
One  of  us  was  exceedingly  surprised  and 
pleased  to  observe  in  a  visit  made  to  the  home 
for  incurables  at  Hawthorne,  N.  Y.,  some  few 
months  ago,  the  wonderful  vitality  exhibited 
by  the  patients  in  this  home  for  incurable  can- 
cer. Several  patients  there  with  cancer  of  the 
stomach  had  been  inmates  from  several 
months  to  several  years,  in  whom,  while  the 
diseased  condition  was  not  cured,  it  had  ap- 


Il8  CANCER 

parently  been  arrested.  In  that  institution, 
outside  of  the  comfortable  hygienic  surround- 
ings, good  nursing,  and  abundant  food  sup- 
ply, the  improvement  could  only  be  attributed 
to  the  abundance  of  fresh  country  air,  the  in- 
stitution being  situated  on  a  hill  a  few  hun- 
dred feet  above  the  sea  level. 

The  probabilities  are  that  these  cases  do 
better  under  the  same  climatic  conditions  as 
tuberculosis  patients  do.  But  so  far  as  we  are 
aware,  statistics  are  lacking  to  show  the  best 
climatic  conditions  for  these  people.  The 
same  rules  should  probably  apply  as  are  found 
the  best  in  sanitariums  for  sufferers  from 
tuberculosis.  They  should  keep  in  the  open 
air  practically  all  the  time,  with  an  abundant 
food  supply,  and  be  provided  with  some  oc- 
cupation so  far  as  the  given  case  permits.  If 
such  conditions  as  frequent  retardation  of  the 
malignant  growth  exists,  as  we  found  in  the 
institution  mentioned  above,  which  is  consid- 
ered a  home  for  incurables,  and  in  which,  so 
far  as  we  are  able  to  observe,  no  medicinal 
treatment  beyond  ordinary  palliative  meas- 
ures was  administered,  what  might  not  be 
hoped  for  in  similar  institutions  if  the  diag- 
nosis was  made  early,  and  a  systematic  method 
of  medicinal  treatment,  in  addition,  carried 


GENERAL  TREATMENT  II9 

out?  Unfortunately,  the  death  rate  in  homes 
for  incurable  cancer  in  the  large  cities  is  ex- 
tremely high.  The  main  reason  for  this  is 
that  patients  are  received  there  practically 
moribund,  and  in  such  a  state  that  their  sys- 
tem has  been  thoroughly  undermined  by  a 
general  carcinomatosis,  with  not  only  one  but 
so  many  infected  processes  at  work  that  ordi- 
narily anything  beyond  the  relief  of  pain  is 
practically  impossible.  Even  in  such  insti- 
tutions, however,  more  attention  to  details  in 
the  carrying  out  of  some  properly  formulated 
and  well-planned  remedial  measures  will 
lower  the  death  rate,  and  very  materially  in- 
crease the  number  of  patients  who  could  be 
discharged  if  not  cured,  at  any  rate  with  the 
diseased  condition  practically  arrested.  At 
present  this  rarely  happens. 

The  food  supply  is  one  concerning  which 
there  has  been  considerable  discussion ;  dietary 
sheets  have  been  compiled  according  to  the 
point  of  view  concerning  the  cause  of  cancer 
which  is  held  by  the  attendant.  It  is  hardly 
our  desire  to  go  into  a  discussion  of  the  vari- 
ous regimens  which  have  been  suggested. 
Up  to  the  present  time  we  are  of  the  opinion 
that  under  ordinary  circumstances  a  mixed 
diet  of  well-cooked  food  is  preferable,  modi- 


120  CANCER 

fied  necessarily  according  to  circumstances 
surrounding  any  given  case.  It  has  been  sug- 
gested by  some,  very  cleverly  and  perhaps 
wisely,  that  an  attempt  should  be  made  to  use 
food  as  free  as  possible  from  sulphur.  An  in- 
teresting article  has  been  written  by  Dr.  Kess- 
ler  concerning  this  sulphur-free  diet  ("Diet 
in  Carcinoma,"  N.  Y.  Med.  Jour.,  1912).  If 
our  view  of  the  sulphur  metabolism  is  the 
correct  one,  the  condition  of  the  individual 
will  neither  be  improved  nor  made  worse  by 
withholding  the  ordinary  amount  of  sulphur 
constituents  from  the  system. 

It  is  hardly  necessary  to  speak  about  bath- 
ing, more  than  to  say  that  it  is  an  advantage 
in  keeping  the  skin  in  as  good  a  condition  as 
possible,  and  above  all  of  value  as  the  cir- 
cumstances surrounding  any  given  case  will 
permit  of  inducing  perspiration  as  a  method 
of  cleaning  the  inside  of  the  skin,  relieving 
the  kidneys,  and  improving  the  general  con- 
dition. In  fact,  some  medicinal  preparations 
used  for  malignant  growth  have  probably 
been  of  benefit  through  their  action  in  stim- 
ulating perspiration. 


CHAPTER    II 

Vanadium  and  Arsenic.  Iron  and  Man- 
ganese. CONDURANGO,  AND  OTHER  BIT- 
TER Tonics 

Having  found  (as  stated  in  previous  chap- 
ters) that  all  oxidizing  agents  properly  ap- 
plied are  of  benefit  in  cancer,  v^e  state,  as  sim- 
ply as  possible,  the  manner  of  using  the  above- 
mentioned  remedies  which  we  have  found 
most  useful,  believing  that  in  so  doing  we 
avoid  going  beyond  the  limitations  of  this 
work  and  invading  the  field  of  polyphar- 
macy. 

It  is  claimed  that  vanadium  is  more  power- 
ful than  arsenic,  while  its  toxic  effects  are 
about  one-tenth  less.  Solutions  of  soluble 
salts  in  strengths  of  from  1-20,000  to  1-50,000 
make  very  good  antiseptics.  Our  experience 
with  vanadium  is  limited,  but  sufficient  to 
make  us  consider  it  worthy  of  further  inves- 
tigation; it  may  prove  to  be  a  much  better 
tonic  than  arsenic.     It  can  also  be  combined 

121 


122  CANCER 

with  selenium,  to  make  salts  of  the  two  ele- 
ments, Vanadium  selenides,  of  which  there 
may  be  several,  di-,  tri-,  tetra-,  penta-sele- 
nides,  V2Se2,  V2Se3,  V2Se4,  V2Se5.  These 
combinations  are  very  insoluble,  and  therefore 
for  internal  use  they  are  unsatisfactory. 
When,  however,  any  of  these  vanadium  sele- 
nides are  combined  with  either  potassium  or 
sodium  they  form  potassium  selenovanadate, 
or  sodium  selenovanadate,  both  of  which  are 
soluble. 

Solutions  of  these  have  been  given  in  doses 
of  from  one  to  two  milligrams  three  times 
daily,  and  it  is  reported  that  satisfactory  re- 
sults have  been  obtained  from  their  use. 

For  external  use,  preparations  of  vanadium 
and  selenium,  the  vanadium  tri-  or  penta- 
selenide,  in  the  form  of  3  per  cent  to  5  per 
cent  ointment,  have  proven  satisfactory.  The 
base  recommended  is  a  combination  of  eu- 
cerine  and  lanoline. 

Within  the  last  few  years  several  prepara- 
tions of  vanadium  by  different  manufacturers 
either  in  this  country  or  abroad  have  ap- 
peared. So  far  they  have  been  used  to  a  very 
limited  extent.  Within  the  last  four  or  five 
years  they  have  received  some  recognition 
either  alone  or  combined  with  other  elements, 


VANADIUM,  ARSENIC,   ETC.  1 23 

as  a  method  of  retarding  growths.  Their  use 
has  been  recommended  for  internal  adminis- 
tration or  for  external  application  for  the 
same  purpose  either  alone  or  combined  with 
selenium,  or  with  an  ointment  base  as  men- 
tioned above.  When  used  combined  with 
selenium  externally  it  has  been  with  the  idea 
of  administering  selenium  through  inunction 
for  its  constitutional  efifects,  and  with  the  idea 
of  making  the  action  of  the  former  less  de- 
pressing. The  exact  action  of  vanadium  has 
not  yet  been  studied  carefully  enough  to  be 
understood,  but  it  probably  has  a  constitu- 
tional efiPect  resembling  that  of  arsenic  more 
closely  than  any  other  element;  acting  as  a 
tonic  and  as  an  antiseptic  in  some  way,  toning 
up  the  cell  by  the  above  measures  and  making 
the  tissues  become  more  resistant  to  bacterial 
invasion.  It  is  never  administered  in  a  metal- 
lic state  internally,  but  always  as  a  soluble  salt, 
and  generally  in  combination  with  some  other 
element  or  acid  radical.  When  administered 
alone  it  is  generally  given  in  the  form  of 
vanadic  acid  or  vanadium  oxychloride  solu- 
tion. We  have  not  had  any  experience  with 
this  element  administered  alone,  but  we  have 
observed  its  efifects  in  several  cases  when  given 
in  one  to  two  milligram  doses  three  times  a 


124  CANCER 

day,  when  administered  as  potassium  seleno- 
vanadate.  This  solution  is  probably  one 
which  is  somewhat  unstable,  and  not  as  easy 
to  obtain  as  colloidal  selenium,  but  in  the  few 
cases  in  which  we  have  tried  it  the  results 
have  apparently  been  as  satisfactory  as  could 
be  expected,  and  no  depressing  after-efifects 
have  been  noticed  to  follow  its  administra- 
tion. 

Vanadium  oxychloride,  vanadium  sul- 
phate, or  any  soluble  salt  has  been  used  for 
antiseptic  solution  in  the  strength  of  1-20,000 
to  1-50,000. 

Arsenic,  since  its  discovery,  has  justified  its 
reputation  as  a  useful  remedy  for  diseases  of 
the  skin,  and  also  as  an  alternative  oxidizing 
tonic  for  the  system  when  administered  in- 
ternally, and  probably  in  some  form  or  other, 
either  externally,  internally,  hypodermically, 
or  intravenously,  is  employed  more  than  any 
other  strictly  medicinal  agent  for  cancer.  In 
our  experience  with  it,  which,  while  some- 
what limited,  has  been  to  a  great  extent  in 
far  advanced  cases,  w^e  have  not  found  it  as 
useful  as  the  proper  preparation  of  selenium, 
vanadium,  and  to  some  extent  tellurium.  But 
aside  from  these  it  seems  about  as  useful  as, 
and  safer  than,  some  of  the  other  more  re- 


VANADIUM,  ARSENIC,   ETC.  1 25 

cently  discovered  methods  for  the  treatment 
of  this  disease. 

It  should  be  noted  that  as  an  oxidizing 
agent  arsenic  and  vanadium  are  concerned 
principally  with  carbon,  and  hydrogen,  while 
oxygen  is  the  compound  with  which  selen- 
ium and  tellurium  are  most  intimately  asso- 
ciated. 

Again,  at  the  risk  of  indulging  in  repeti- 
tion, we  wish  to  call  attention  to  the  fact  that 
there  is  a  wonderful  resemblance  in  cases  of 
old  syphilis  and  of  cancer;  in  some  form  they 
seem  to  be  cousins,  and  while  arsenic  gives 
very  brilliant  results  when  administered  in- 
ternally, or  especially  intravenously  in  the 
form  of  salvarsan,  very  great  care  indeed 
should  be  used  to  be  sure  that  a  proper  differ- 
entiation has  been  made  between  these  two 
diseases.  Arsenic  in  the  form  of  salvarsan, 
neosalvarsan,  or  some  of  its  substitutes, 
should,  when  practicable,  be  administered  in 
two  large  doses  at  intervals  of  a  week,  and  its 
effect  watched  in  all  doubtful  cases,  and  in 
those  in  which  the  slightest  uncertainty  ex- 
ists, even  if  a  month's  previous  treatment  by 
means  of  mercury  and  the  iodides  has  caused 
no  effect.  Salvarsan  and  neosalvarsan  have 
been  used  as  remedies  for  undoubted  carcin- 


126  CANCER 

oma  itself,  with  apparently  occasional  bene- 
fit, and  recently  they  have  been  recommended 
by  such  an  exhaustive  writer  on  the  subject 
as  Roncali  (Trattato  di  Neoplasmi  Maligni, 
Torino,  1916).  He  finds  its  administration 
more  efficacious  in  the  connective-tissue  than 
in  the  epithelium  growth. 

In  the  administration  of  arsenic  internally 
as  an  oxidizing  tonic,  ordinarily  we  prescribe 
a  fifth  of  a  grain  of  arsenous  acid  in  the  form 
of  a  freshly  made  pill  dusted  over  with  black 
pepper,  three  or  more  times  a  day;  this  is  the 
^Til.  Asiatica"  of  the  old  pharmacopoeias. 
We  have  not  infrequently  found  arsenous  acid 
paste  of  great  value  as  an  external  application 
to  epithelioma  of  the  skin,  naturally  not  the 
mucous  membranes ;  we  have  sometimes  found 
this  apparently  of  more  benefit  than  excision, 
particularly  in  places  like  the  angle  of  the 
eye,  where  excision  was  a  difficult  and  awk- 
ward operation  to  perform,  and  it  has  also 
been  of  great  use  in  cases  of  epithelioma  after 
the  application  of  radium  and  the  X-ray 
had  proved  inefficient.  We  use  the  paste,  of 
which  the  following  is  the  formula: 


VANADIUM,  ARSENIC,   ETC.  1 27 

Arsenic  Paste 
Acid  arsenous,  one-half  dram. 
Amylum,  \ 

Powdered  alum,    v  of  each,  two  drams 
Glycerine,  ) 

Distilled  water,  one-half  dram. 
Mix. 

This  is  approximately  7  per  cent;  we  also 
use  it  in  a  strength  of  10  per  cent  and  15  per 
cent.  If  this  paste  becomes  too  hard  for  ap- 
plication it  should  be  warmed,  before  using, 
in  a  warm  bath;  a  little  hot  water  may  also 
be  added.  It  is  sometimes  difficult  to  tell 
which  strength  is  the  best  adapted  for  the  in- 
dividual until  two  or  three  have  been  tried 
out.  The  application  should  be  of  a  strength 
sufficient  to  cause  reaction,  such  as  swelling, 
reddening,  and  possibly  some  increase  in  dis- 
charge, for  from  one  to  two  weeks  after  its 
application,  during  which  time  some  simple 
ointment  like  cold  cream  should  be  applied, 
and  when  the  reaction  has  entirely  subsided 
another  application  should  be  made  of  the 
same  strength  or  stronger,  as  is  held  to  be  the 
correct  view  for  the  particular  case.  This 
paste  should  simply  be  painted  over  the  sur- 
face  of   the   ulcerated   area,   not  beyond  it, 


128  CANCER 

lightly  but  thoroughly,  with  a  cotton  or 
wooden  applicator,  once.  The  reaction  will 
start  immediately.  But  again  attention  must 
be  called  to  the  fact  that  where  the  external 
applications  of  arsenous  acid  paste  seem  to 
be  of  great  benefit  it  is  well  to  combine  with 
them  the  internal  administration  of  selenium 
and  vanadium  or  some  other  of  the  oxidizing 
elements  of  like  nature  already  mentioned. 
Where  it  is  not  practicable  to  obtain  these  in 
their  proper  form  arsenic  should  also  be  ad- 
ministered internally  as  well  as  externally, 
and  with  the  proper  periods  of  rest,  so  as  to 
avoid  its  cumulative  effects  during  the  re- 
maining lifetime  of  the  patient. 

Iron,  the  well-known  oxidizer  when  admin- 
istered in  such  form  as  not  to  irritate,  is  of 
great  value  in  cases  of  carcinoma,  in  associa- 
tion with  whatever  other  methods  may  be 
tried,  except  possibly  some  of  the  newer  oxi- 
dizing agents  mentioned,  which  apparently 
do  better  when  administered  by  themselves. 
Naturally  enough,  in  cases  far  advanced,  it 
has  been  noted  by  others  (and  written  about) 
that  a  profound  anemia  is  apt  to  exist  with  a 
marked  carcinomatosis;  in  this  condition, 
with  the  exception  mentioned  above,  like 
other  oxidizing  substances,  iron  is  indicated. 


VANADIUM,  ARSENIC,   ETC.  1 29 

in  addition  to  that  even  where  the  blood- 
count  or  hemoglobin  are  not  materially  re- 
duced. It  is  well  to  use  it  in  whatever  form 
is  found  to  be  the  least  irritating;  as,  tartrate 
of  iron  and  potassium,  or  as  a  peptonate,  or 
it  can  be  combined  with  manganese,  which 
deservedly  enjoys  a  reputation  as  an  oxidizing 
agent.  This  may  be  administered  with  iron, 
or  separately,  often,  and  in  as  large  a  dose  as 
can  be  borne  without  causing  irritation,  and 
for  long  periods  of  time.  The  idea  being 
that  all  of  the  above,  together  with  the  proper 
hygienic  surroundings,  excision,  radium,  X- 
ray,  or  other  agents,  may  help  to  retard  the 
growth  of  the  cancer,  even  if  it  is  not  cured; 
so  that  the  individual  may  live  in  compara- 
tive ease,  and  possibly  die  of  some  intercur- 
rent disease  which  is  apt  to  cause  less  suffer- 
ing than  cancer. 

We  now  come  to  consider  a  class  of  reme- 
dies concerning  the  therapeutic  effects  of 
which  but  little  is  known;  but  as  a  result  of 
our  observations  we  believe  that  some  of  them 
are  of  service;  but  in  what  way  they  are  a 
benefit  is  a  problem  for  the  physiological 
chemist  to  work  out.  Since  the  beginning  of 
time,  apparently,  herbs  of  various  kinds  have 
enjoyed  a  reputation  for  their  beneficial  ef- 


130  CANCER 

fects  on  cancer.  This  has  been  particularly 
true  among  natives  in  inaccessible  regions, 
where  medical  aid  has  been  hard  to  obtain. 
It  is  interesting  to  note  that  they  often  have  a 
remedy  for  snake-bite  and  for  cancer.  Gen- 
erally, they  are  found  to  be  preparations 
which  induce  perspiration.  Dried  violet 
flowers,  in  our  observation,  seems  to  have  been 
the  favorite  in  this  respect;  made  into  a  tea 
and  drunk  freely,  it  certainly  seems  a  useful 
remedy  to  induce  perspiration,  and  has  been 
recommended  by  some  scientific  workers  as 
useful  for  certain  forms  of  skin  disease.  The 
tea  made  from  hemlock  buds,  also,  has  its 
reputation,  but  in  this  the  amount  of  resin  is 
considerable,  and  is  liable  to  cause  gastric 
irritation.  There  are  some  two  or  three  bit- 
ter tonics  which  we  have  used  that  have  ap- 
parently been  of  benefit,  whether  by  increas- 
ing tissue  metamorphosis  in  such  a  way  as  to 
help  oxidize  the  amount  of  neutral  sulphur 
apparently  always  present,  or  whether  simply 
by  stimulating  the  digestive  organs  so  that 
they  aid  in  assimilation  of  food,  is  beyond  our 
knowledge.  Of  these,  condurango  occupies 
the  first  place;  echinacea  administered  with 
it  may  or  may  not  add  to  its  value.  We  have, 
therefore,  been  in  the  habit  of  administering 


VANADIUM,  ARSENIC,   ETC.  I31 

to  those  cancer  patients,  where  we  have  not 
been  able  to  obtain  the  other  oxidizers  which 
we  have  found  to  occupy  the  first  rank  (as 
selenium  and  vanadium),  the  bitter  tonic  of 
which  the  following  is  the  formula: 

Bitter  Tonic 
Gondurango  bark, 

Sarsaparilla  root,  ,     .       1    1    ir 
^11  ,         /  01  each,  hall  ounce 

Columbo  root,        \  ' 

Echinacea, 

Boiling  water,  enough  to  make  one  pint. 

Make  infusion,  and  filter. 

Dose:  Half  ounce  in  water  half  hour 

before  meals. 

We  have  found  it  to  be  well  borne  and  of 
apparent  benefit,  even  by  those  suffering  from 
profound  general  carcinomatosis;  although, 
of  course,  it  is  not  recommended  in  any  way 
as  a  cure-all.  For  the  skilful  preparation  of 
this,  as  well  as  the  arsenous  acid  paste  recom- 
mended above,  we  are  indebted  to  the  kind 
offices  of  our  friend,  Mr.  Louis  Protzmann, 
a  well-known  pharmaceutical  chemist  of  this 
city. 


CHAPTER    III 

Radium,  X-ray 

The  more  the  investigator  carefully  exam- 
ines the  evidence  furnished  by  the  later  meth- 
ods of  the  treatment  of  malignant  growths, 
and  separates  out  as  far  as  possible  from  such 
evidence  the  mass  of  conflicting  testimony, 
both  pro  and  con,  which  must  be  thrown  aside 
from  the  unreliability  of  its  source  (this  term 
being  used  to  cover  irregularities  in  reports 
due  to  varying  causes),  the  more  forcibly  is 
the  investigator  confirmed  in  any  views  held 
as  to  the  constitutional  character  of  carci- 
noma, and  the  more  profound  is  the  convic- 
tion that  the  varying  lesions  treated  are,  and 
can  only  be,  local  manifestations  from  consti- 
tutional disturbance.  Among  the  later  and 
most  carefully  worked  out  are  the  treatments 
of  such  lesions  by  radium  and  the  X-ray,  In 
the  fourth  edition  of  the  work  of  Greene  and 
Brooks,  IQ17,  previously  referred  to,  the 
statement  is  made  that  radium  has  come  to 
stay.    Since  its  publication  further  experience 

132 


RADIUM  AND  X-RAY  1 33 

and  consideration  of  cases  previously  treated 
has  not  made  it  necessary  to  attempt  to  modify 
that  statement.  But  like  many  other  proce- 
dures, both  surgical  and  medical,  which  have 
been  heralded  with  considerable  enthusiasm, 
too  much  has  been  claimed  for  radium  on  the 
one  hand,  and  on  the  other  hand  scepticism 
has  been  too  pronounced.  Attention  is  called 
to  a  conscientious  and  scientific  work  recently 
published,  "Radium  Therapy  and  Cancer," 
by  Henry  H.  Janeway,  M.D.,  Benjamin  So 
Barringer,  M.D.,  and  Ghoacchino  Failla, 
E.E.,  A.M.,  published  by  Paul  B.  Hoeber, 
New  York,  1917.  Particularly  to  be  read 
are  the  general  conclusions  of  Dr.  Janeway, 
page  222.  Our  conclusions  concerning  the 
value  of  the  use  of  this  element  up  to  the 
present  time  are  as  follows:  that  radium,  like 
other  factors  that  can  be  employed,  will  not 
cure  cancer.  It  will  sometimes  cure  lesions 
caused  by  cancer,  and  by  so  doing  retard  can- 
cer better  than  any  other  agent  that  can  be 
used.  Its  use  seems  to  be  of  particular  benefit 
in  cancer  of  the  mucous  membranes.  Our  own 
experience  in  the  use  of  this  substance,  either 
when  demonstrated  in  our  own  cases  or  in 
cases  which  have  come  under  our  observation, 
has  not  been  extensive.     On  the  other  hand, 


134  CANCER 

it  has  been  interesting,  and  has  covered  fairly 
well  quite  a  few  lesions  due  to  cancer  of  va- 
rious types,  and  also  such  a  sufficient  period 
of  time  that  that  valuable  factor  has  helped 
us  in  the  formation  of  our  conclusions. 

Very  little,  purposely,  has  been  recorded  in 
this  volume  regarding  individual  cases;  but 
just  here  space  will  be  occupied  in  mention- 
ing a  few  cases  which  demonstrate  the  char- 
acteristic effects  of  radium.  Two  of  the 
younger  men  associated  with  us  at  the  time 
were  the  first  in  this  country,  so  far  as  we  are 
aware,  to  try  radium  for  carcinoma  of  the 
bladder.  A  few  months  after  the  radium  had 
been  applied,  the  application  in  each  case 
having  been  made  through  a  supra-pubic  in- 
cision, the  cases  were  reported  at  the  New 
York  Academy  of  Medicine  and  published 
("Application  of  Radium  in  the  Bladder  for 
Carcinoma,  with  Report  of  Two  Cases,"  F.  J. 
Schoenenberger,  M.D.,  and  William  Scha- 
pira,  M.D.,  The  Journal  of  the  American 
Medical  Association) .  One  of  these  patients 
died,  apparently  from  metastasis  in  the  kid- 
ney, about  six  months  after  the  application  of 
the  radium,  the  bladder  in  the  meantime  hav- 
ing been  apparently  cured.  The  bladder  le- 
sion in  the  second  case  was  also  apparently 


RADIUM  AND  X-RAY  1 35 

cured,  the  man  gained  many  pounds  in 
weight,  cystoscopic  examination  failed  to 
show  anything  but  a  scar  where  the  growth 
had  been,  and  in  this  case  part  of  the  growth 
had  been  removed  by  excision  for  microscopi- 
cal examination.  He  continued  in  this  con- 
dition for  two  years,  at  the  end  of  which  time 
he  was  lost  sight  of.  At  the  end  of  three  years 
he  appeared  in  the  wards  of  the  hospital  with 
which  one  of  us  is  connected,  with  an  exten- 
sive reappearance  of  the  cancer  of  the  blad- 
der, at  the  seat  of  the  previous  lesion,  and 
died  under  our  observation  within  a  few 
weeks.  Another  interesting  case  was  that  of 
a  woman  who  came  under  our  care,  for  a 
small  papillomatous  growth,  appearing  six 
months  after  an  operation  for  the  removal  of 
the  uterus  and  ovaries,  through  the  vagina. 
The  diagnosis  was  confirmed  by  microscopi- 
cal examination.  When  a  papilloma  ap- 
peared in  the  vagina  at  the  apex  of  the  old 
scar  the  case  was  referred  from  the  hospital 
in  which  she  had  been  operated  on  to  a  home 
for  incurables,  and  on  account  of  the  hemor- 
rhage was  referred  to  one  of  us.  Cauteriza- 
tion had  no  effect  on  this  growth.  The  pa- 
tient was  very  thin  and  weak;  hemoglobin 
50  per  cent,  Wassermann  negative,  cachectic 


136  CANCER 

appearanceo  Finding  other  measures  give  no 
relief,  two  applications  of  radium  emanations 
were  made.  About  two  weeks  after  the  first 
one  the  growth,  which  was  about  the  size  of 
the  end  of  the  little  finger,  disappeared.  The 
hemorrhages  ceased,  the  woman  lived  a  year, 
and  then  died,  apparently  from  a  general  car- 
cinomatosis. It  was  impossible  to  obtain  an 
autopsy.  In  this  case  it  seems  undoubted,  as 
in  the  one  recorded  above,  that  the  use  of  ra- 
dium prolonged  life. 

At  the  present  time  cancer  therapy  by 
means  of  radium  is  so  associated  with  its 
treatment  by  X-ray  that  the  two  should  prob- 
ably be  considered  together.  To  a  consid- 
erable extent  the  nature  of  the  treatment  is 
the  same,  and  it  is  also  true  that  a  persistent 
search  is  being  made  with  both  of  these  meth- 
ods to  find  out  more  about  the  laws  under 
which  they  work,  the  right  dosage  of  both  for 
any  given  case,  and  the  safeguards  to  be  em- 
ployed in  their  use. 

Radium  can  be  made  to  penetrate  the  tis- 
sues deeper  than  the  X-ray,  and  naturally  is 
much  more  expensive  to  use,  and  more  diffi- 
cult to  obtain.  Following  operations  for  such 
conditions  as  carcinoma  of  the  breast,  one  or 
two  applications  of  radium  may  be  made,  fol- 


RADIUM  AND  X-RAY  1 37 

lowed  later  on  by  a  more  diffuse  and  general 
application  of  the  X-ray  over  the  medias- 
tinum and  adjacent  parts.  In  other  words, 
the  X-ray  is  apparently  being  used  more  dif- 
fusely now  than  was  the  former  custom  whei/ 
X-ray  applications  were  first  applied. 

Attention  is  being  called  to  the  very  in- 
genious methods  of  Dr.  Murphy,  of  the 
Rockefeller  Institute,  concerning  which  com- 
paratively little  has  been  written  ("Hetero- 
plastic Tissue  Grafting  through  Roentgen- 
Ray  Lymphoid  Destruction,"  The  Journal 
of  the  American  Medical  Association,  1917). 
His  method,  as  we  understand  it,  consists  in 
the  application  of  comparatively  mild  doses 
of  the  X-ray  upon  such  conditions  as  carcin- 
oma recurring  in  old  scars  following  exci- 
sion, the  strength  and  frequency  of  the  appli- 
cation being  regulated  by  its  effect  upon  the 
lymphatics.  The  idea  being  that  in  mild 
doses  its  application  may  encourage  lympho- 
cytosis, and  through  that  means  have  an  in- 
hibitory effect  upon  the  growth;  whereas,  if 
the  strength  of  the  application  was  too  severe 
it  would  be  shown  by  the  destruction  of  these 
elements,  and  through  this  measure  increase 
the  activity  of  the  malignant  processes.  It  can 
be  safely  stated  that  so  far  the  beneficial  ac- 


138  CANCER 

tion  of  the  X-ray  in  its  various  forms  seems 
to  be  confined  almost  entirely  to  smaller  le- 
sions, particularly  those  upon  the  skin,  and 
that  its  use  apparently  has  never  been  demon- 
strated to  be  of  any  great  value  for  the  deeper- 
seated  lesions,  like  those  in  the  mediastinal 
glands;  but  experiments  in  this  latter  direc- 
tion are  being  made,  as  mentioned  above. 

If  our  conception  of  malignant  growths  is 
correct,  as  we  believe  it  is,  to  the  extent  that 
we  have  expressed  it,  that  carcinoma  is  a  con- 
stitutional disease,  it  would  not  be  expected, 
then,  that  X-ray  therapy  would  have  any 
greatly  beneficial  effect  upon  it,  more  than  to 
be  of  considerable  aid  in  certain  of  its  skin 
manifestations.  Under  such  limitations  it 
would  seem  to  us  as  if  the  method  suggested 
by  Dr.  Murphy  is  a  valuable  one,  and  that 
in  certain  cases  beneficial  results  might  be 
expected  to  follow  its  administration  in  the 
manner  suggested  by  him.  Fulguration  also 
has,  we  believe,  a  useful  field  (but  one  not 
yet  clearly  defined)  in  the  removal  of  small 
growths  either  on  the  skin  or  mucous  mem- 
branes. 


CHAPTER    IV 

Excision 

The  value  of  excision  as  a  therapeutic 
measure  in  various  forms  of  cancer  is  a  some- 
what difficult  one  to  write  about,  as  so  many 
perplexing  questions  necessarily  arise  in  con- 
nection with  it.  Among  others,  is  the  proper 
amount  of  consideration  to  be  given  to  vari- 
ous divergent  views.  The  road  is  a  long  one 
between  the  views  of  those  who  believe  that 
''cancer  can  be  cured  without  a  knife"  and 
those  who  advocate  the  removal  of  large 
areas  of  tissue  and  all  lymphatic  glands  pos- 
sible to  be  found  in  the  vicinity  of  the  growth, 
and  even  go  so  far  as  to  recommend  such  pro- 
cedures as  female  castration  for  carcinoma  of 
the  breast. 

It  will  be  easier  for  those  who  have  read 
the  preceding  chapters  to  understand  our 
views,  which  are  founded  not  only  on  our  own 
belief  in  the  nature  of  the  processes  to  be 
dwelt  with,  previously  recorded,  but  also  on 
the  results  of  our  clinical  observations  and 

139 


140  CANCER 

experience  in  surgical  procedures;  and  while 
to  some  degree  they  may  diverge  from  the  ex- 
treme views  held  by  many,  they  also  to  a  con- 
siderable extent  tend  to  bring  many  of  the 
divergent  views  into  a  certain  amount  of  ac- 
cord. 

We  realize  that,  in  making  the  statement 
that  the  value  of  excision  for  a  growth  as  a 
therapeutic  measure  will  depend  upon  the 
circumstances  surrounding  each  given  case, 
we  offer  nothing  new.  But  the  refinements  of 
diagnosis  now  at  the  command  of  the  surgeon, 
to  which  we  have  endeavored  to  make  some 
contribution  on  our  part,  enable  him  to  un- 
derstand the  circumstances  which  surround 
any  individual  case  much  more  clearly  than 
would  have  been  possible  a  few  years  ago. 
We  make  the  statement  clearly  that,  in  our 
belief,  "no  operation  will  cure  cancer."  On 
the  other  hand,  a  statement  can  be  made  with 
equal  truth  that  the  proper  operative  proce- 
dures will  often  retard  its  active  development 
to  such  an  extent  that  the  individual's  life  can 
be  prolonged  for  many  years,  so  that  they 
may  die  from  some  intercurrent  disease,  and 
that  they  are  often  our  best  therapeutic  pro- 
cedure. 

Whatever  may  be  its  finer,  primary,  patho- 


EXCISION  141 

logical,  or  original  cause — that  cancer  (like 
syphilis  or  tuberculosis)  is  a  constitutional 
disease,  there  seems  to  us  no  doubt;  and  oper- 
ations for  the  cure  of  cancer  no  more  cure  can- 
cer, however  much  they  may  retard  it,  than 
does  the  removal  of  a  tuberculous  kidney  cure 
tuberculosis;  although  both  may  be  of  help 
to  the  individual.  Possibly  the  removal  of  a 
gumma  might,  and  probably  often  has,  when 
it  has  been  removed  through  a  mistake  in 
diagnosis,  aided  in  the  same  way  a  syphilitic 
individual. 

The  factors  to  be  considered  in  determining 
the  character  of  the  operation  to  be  performed 
are:  (i)  heredity;  (2)  nature  of  the  growth ; 
(3)  extent  of  the  growth,  particularly  as  de- 
termined by  carefully  taken  skiographic  pic- 
tures; (4)  previous  treatment;  and  (5)  the 
general  condition  of  the  patient. 

A  consideration  of  the  above  should  tend 
to  modify  the  decision  as  to  the  operation  and 
its  character. 

The  above  refers  to  operative  procedures 
for  primary  and  generally  extensive  lesions 
of  cancer,  when  of  more  than  a  palliative 
character.  The  indications  for  these  latter 
are  often  present,  and  naturally  they  fre- 
quently are,  and  should  be  undertaken  for  the 


\ 


142  CANCER 

purpose,  if  not  of  prolonging  life  to  any  great 
extent,  for  the  relief  of  hemorrhage,  pain,  and 
general  discomfort.  In  connection  with  oper- 
ations, and  basing  our  opinions  not  only  on 
the  results  of  our  own,  but  that  observed  from 
the  surgical  work  of  others,  we  believe  that 
the  mistake  more  often  made  than  any  other 
is  the  neglect  of  the  after  constitutional  treat- 
ment of  patients,  following  whatever  opera- 
tive procedure  may  have  been  instituted, 
whether  with  the  hope  of  a  radical  cure  or  as 
a  palliative  measure.  The  details  of  such 
treatment  are  recorded  in  other  chapters  of 
this  w^ork.  This  neglect  is  evidently  based  on 
a  very  general  misconception  (which  how- 
ever, is,  we  believe,  being  gradually  over- 
come) of  the  nature  of  the  disease. 

That  the  above  statement  is  correct  will  be 
forcibly  impressed  upon  those  observers  who 
have  been  given  the  opportunity  to  carefully 
examine  cases  which  come  to  institutions  that 
are  intended  for  the  treatment  of  malignant 
grow^ths;  and,  above  all,  those  who  have  ob- 
served condition  of  affairs  as  they  exist  in  the 
various  homes  for  incurables.  Even  in  these 
latter,  there  is  a  tendency  to  too  much  laxity 
in  careful  history  taking  and  supervision  of 
both  hygienic  and  medicinal  remedial  meas- 


EXCISION  143 

ures.  Not  infrequently  in  them  are  the  proper 
measures  for  diagnosis  overlooked,  and  care- 
lessness used  in  the  methods  to  differentiate 
malignant  growths  from  the  later  lesions  of 
syphilis,  which  could  be  easily  benefited  by 
constitutional  measures.  In  such  institutions 
suffering  should  be  ameliorated  by  the  proper 
application  of  every  suitable  remedy,  both 
external  and  internal.  In  addition  to  the 
above,  by  proper  laboratory,  out-patient,  and 
autopsical  work,  some  of  these  places  which 
are  now  used  mainly  as  homes  for  the  un- 
fortunate to  die  in  would  become,  in  addition, 
centers  for  scientific  research,  and  thus  aid  in 
the  discovery  of  new  methods  for  the  combat- 
ing of  disease. 

In  closing  this  chapter  we  wish  again  to 
emphasize  the  fact  that  in  any  given  case,  be- 
fore operating,  the  surgeon  should  be  sure  that 
he  has  used,  if  not  all,  at  least  all  practicable 
diagnostic  procedures  that  are  at  hand,  among 
the  most  important  of  which  may  be  again 
mentioned  the  necessity  of  a  stereoscopic  X- 
ray  picture,  and,  when  possible,  examination 
of  the  sulphur  contents  of  the  blood  and  urine. 


CHAPTER   V 

Selenium  and  Tellurium 

Mendeleeff  has  divided  all  the  elements 
into  groups  according  to  their  atomic  weights 
and  properties.  According  to  this  classifica- 
tion it  appears  that  the  properties  of  the  ele- 
ments bear  the  same  relation  to  one  another 
as  that  manifested  by  the  atomic  weights. 
According  to  this  grouping,  selenium  is  placed 
in  the  same  group  with  sulphur,  which  means 
that  its  properties,  chemical  and  physical, 
are  analogous  to  that  of  sulphur.  In  addi- 
tion to  the  chemical  and  physical  properties 
of  these  elements,  we  find  that  their  biochem- 
ical properties  depend  as  well  upon  the 
grouping  of  Mendeleeff.  In  its  physical 
forms  selenium  closely  resembles  sulphur; 
that  is,  it  may  assume  several  allotropic  forms, 
but,  however,  it  differs  from  sulphur  in  the 
fact  that  it  is  a  metal.  Like  sulphur,  it  forms 
binary  compounds,  analogous  to  the  sulphides. 
These  compounds  are  called  selenides.  In  its 
metallic  form  it  forms  salts,  and  one  of  the 

144 


SELENIUM  AND  TELLURIUM  1 45 

most  interesting  compounds  of  this  type  is  the 
sulpho-cyanate.  The  compound  of  selenium 
that  oxidizes  possesses  colloidal  properties 
and  is  generally  referred  to  as  colloidal 
selenium. 

The  fact  that  selenium  and  sulphur  belong 
to  the  same  group  means  that  selenium  has 
the  property  of  replacing  sulphur  compounds, 
and  this  fact  is  of  extreme  importance  in  its 
biological  relations.  Only  a  limited  amount 
of  work  has  been  done  upon  the  biochemical 
properties  of  selenium  and  selenium  salts. 
They  are  chiefly  stated  as  follows:  If  selenous 
salts  are  administered,  they  are  excreted  in 
the  urine  as  such.  On  the  contrary,  if  selenic 
salts  are  given,  the  selenium  is  excreted  in 
the  form  of  selenous  compounds;  this  means 
that  selenic  salts  have  been  deprived  of  their 
oxygen,  and  this  oxygen  has  been  utilized  in 
oxidation  processes  within  the  body.  Further, 
it  has  been  observed  that  this  oxidation  by 
the  selenic  salts  is  confined  principally  to  sul- 
phur compounds.  On  the  other  hand,  arsenic 
and  vanadium  in  their  compounds  may  act  as 
oxidizing  agents,  but  their  oxidation  is  con- 
cerned principally  with  carbon  and  hydrogen. 

Another  interesting  fact  concerning  the 
effect  of  selenium  salts  upon  the  organism  has 


146  CANCER 

been  demonstrated  by  Wassermann.  He  ob- 
served that  the  administration  of  selenium 
salts  led  to  an  increased  output  of  uric  acid, 
urea,  and  creatinine.  In  confirmation  of  these 
investigations  we  must  state  that  our  results, 
obtained  from  the  blood  of  a  patient  receiv- 
ing the  selenium  compound,  has  shown  that 
the  concentration  of  uric  acid  in  the  blood 
was  far  below  normal,  that  is,  less  than  .5  of 
a  milligram  to  100  c.c,  and  likewise  the 
amount  of  urea  and  creatinine  in  the  blood 
was  abnormally  low.  This  means  that  the 
kidneys  were  stimulated  to  increased  activity. 
Selenium  compounds  likewise  produce  a 
phagocytosis,  a  fact  of  great  importance 
therapeutically  where  we  are  dealing  with  an 
infection  superimposed  upon  a  carcinomatous 
condition. 

The  most  important  problem  presented  to 
the  chemist  in  the  therapeutic  application  of 
selenium  compounds  is  the  elaboration  of  a 
product  of  selenium  which  is  soluble,  easily 
assimilated,  and  non-poisonous.  Selenium  it- 
self is  not  soluble,  and  therefore  is  of  little 
value.  All  the  salts  employed  by  Wasser- 
mann were,  on  continued  application,  toxic. 
But  later  investigations  have  shown  that  it 
is  possible  to   produce  compounds  with  no 


SELENIUM  AND  TELLURIUM  1 47 

toxic  properties.  The  most  commonly  em- 
ployed compounds  are  potassium  seleno-cya- 
nate.  This  compound  is  analogous  to  the 
sulpho-cyanate  of  potassium.  However,  the 
selenium  is  taking  the  place  of  the  sulphur. 
We  do  not  recommend  the  use  of  the  seleno- 
cyanates,  except  with  extraordinary  caution, 
inasmuch  as  they  contain  the  CN  group,  and 
they  have  been  observed  to  have  a  cardiac 
depressant  effect.  If  we  wish  to  effect  a  com- 
plete oxidation,  and  therefore  an  excretion  in 
an  innocuous  form  of  the  product  which  we 
have  observed  in  the  blood,  the  increased 
sulphur  and  non-protein  content,  the  most 
logical  therapeutic  agent  to  apply  is  the  com- 
pound of  selenium  and  vanadium  with  potas- 
sium, commonly  known  as  potassium  seleno- 
vanadate.  In  this  compound  the  oxidation  of 
the  sulphur  and  nitrogen  is  effected  by  the 
selenium,  while  the  oxidation  of  the  carbon 
and  hydrogen  is  brought  about  by  the  va- 
nadium. In  addition  to  the  fact  that  the 
selenium  has  the  effect  of  a  diuretic,  and  al- 
though little  is  known  concerning  the  potash 
metabolism  in  carcinomatous  conditions,  from 
the  results  obtained  it  is  safe  to  say  that  the 
administration  of  potash  salts  is  apt  to  be 
followed  by  an  improvement  in  the  condition. 


148  CANCER 

While    the    administration    of    the    above 
preparation  has  been  attended  with  good  re- 
sults, when  administered  in  the  form  of   a 
solution,  probably  for  ordinary  commercial 
purposes,  it  is  not  as  practical,  and  its  thera- 
peutic properties  will  not  be  preserved  for 
as  long  a  period  as  if  it  is  administered  in 
the  form  of  a  tablet,  of  colloidal  selenium, 
with   the   action   of  which  we   are   also   fa- 
miliar.    It  may  be  used  in  administration  by 
mouth,   by   injection   intravenously,    and   in- 
tramuscularly.   Our  results  lead  us  to  recom- 
mend the  oral  administration.     During  the 
intake  of  selenium  salts  the  sulphur  excretion 
of  the  patient  must  be  carefully  observed.    It 
will  be  noted  that  an  increased  output  of  the 
sulphates  with  a   corresponding  decrease  of 
the  neutral  sulphur  closely  follows  the  ad- 
ministration of  selenium.    The  point  will  be 
reached  where   the   intake   of   selenium   has 
become  so  great  that  it  is  no  longer  fixed  in 
the  tissues  or  utilized  in  oxidation.     It  may 
then  be  detected  in  the  urine  in  the  form  of 
the  hydrogen  compound.    Hydrogen  selenide 
has    a   very    disagreeable    penetrating   odor, 
suggestive   of    decayed   horseradish,    and    its 
presence  in  the  urine  may  be  readily  detected 
in  this  manner.    At  the  same  time  the  patient 


SELENIUM  AND  TELLURIUM  1 49 

will  complain  of  a  continuous  bad  taste  in 
the  mouth.  At  this  point  the  selenium  ad- 
ministration should  be  discontinued  until  the 
selenium  is  no  longer  excreted,  and  then  the 
selenium  compound  may  be  given  a  second 
time  in  small  doses  and  at  longer  intervals. 
Histo-chemical  studies  have  shown  that  se- 
lenium is  assimilated  by  the  tissue  cells,  and 
principally  by  the  cells  of  a  malignant  neo- 
plasm. Following  this  fixation  of  selenium 
a  diminution  in  the  size  of  the  neoplasm  and 
of  the  malignant  character  of  its  cells  may 
be  noted.  Furthermore,  a  fact  of  extreme 
importance  in  dealing  with  advanced  cancers 
is  that  selenium  administration  is  character- 
ized by  a  decrease  in  the  intensity  of  pain. 
During  the  administration  of  selenium  we 
have  found  it  wise  to  gradually  diminish  the 
amount  of  morphine  taken  by  the  patient,  be- 
cause the  intake  of  morphine  is  a  disturbing 
factor,  and,  in  fact,  after  a  time  the  adminis- 
tration of  morphine  may  become  unnecessary. 
In  dealing  with  malignancies  of  the  blad- 
der, hematuria  is  either  a  constant  or  in- 
termittent factor.  The  administration  of 
selenium  often  decreases  this  hematuria. 
Most  probably  this  is  due  to  an  astringent 
action  of  the  compound. 


I50  CANCER 

We  have  observed  the  effects  of  selenium 
on  inoperable  cases,  and  also  following  opera- 
tion in  cases  of  extensive  malignancy,  as  well 
as  in  cases  of  comparatively  mild  cancerous 
invasion,  such  as  a  small  epithelioma  of  the 
skin;  and  we  believe  that  it  has  properties 
which,  if  thoroughly  understood  and  studied, 
will  result  in  its  administration  universally 
and  extensively  to  prevent  the  occurrence  of 
pain  in  pre-cancerous  cases,  and  to  relieve  the 
pain  and  retard  the  growth  of  those  cases 
which  are  further  advanced.  It  has  been  sup- 
posed to  render  certain  inoperable  cases  oper- 
able, but  so  far  such  cases  have  not  come  un- 
der our  direct  observation. 

We  have  used  several  different  preparations 
of  selenium.  Some  of  them  have  a  depressing 
effect  upon  the  heart,  as  has  been  previously 
mentioned,  and  the  various  cyanides  of  se- 
lenium should  not  be  administered  internally 
on  account  of  the  latter  effect.  Selenium  may 
be  used  in  the  form  of  an  inunction,  in  an 
ointment  base,  to  obtain  its  constitutional  ef- 
fects; if  so  desired  it  can  be  used  for  that  pur- 
pose, as  there  are  at  the  present  time  on  the 
market  some  preparations  of  selenium  with 
an  easily  absorbable  ointment  base,  combined 
with  vanadium.    This  is,  however,  a  somewhat 


SELENIUM  AND  TELLURIUM  151 

uncertain  method  of  administration  and  it  is 
locally  irritating  when  it  comes  in  contact 
with  an  ulcerated  surface.  As  a  result  of  our 
investigations  we  recommend  the  internal  ad- 
ministration of  colloidal  selenium.  Colloidal 
selenium  has  been  furnished  us  in  the  form 
of  a  tablet  combined  with  a  physiological 
salt,  in  which  it  is  stated  that  the  sodium  of 
the  salt  has  been  replaced  by  potassium;  there 
is  one  and  one-half  milligram  of  colloidal 
selenium  in  each  tablet.  We  believe  the  po- 
tassium salts  are  the  best  for  this  purpose. 
These  tablets  give  no  depressing  after-effects. 
They  should  be  administered  in  somewhat  the 
same  manner  that  mercury  is  given  for  syph- 
ilis. Ordinarily  the  dose  should  be  increased 
until  the  toxic  effects  of  the  selenium  are  ap- 
parent; two  tablets  after  meals,  three  times 
a  day  for  one  week  in  the  beginning,  then  one 
tablet  three  times  daily  for  one  week  until  the 
system  becomes  saturated  with  selenium.  By 
this  we  mean  that  the  degree  of  oxidation 
will  be  continuous,  theoretically,  as  shown  by 
its  effects  in  reducing  the  amount  of  neutral 
sulphur  in  the  urine,  which  should  be  ob- 
served weekly  for  this  purpose.  Any  toxic 
effects  of  selenium  generally  show  themselves 
by  a  garlicky  odor  to  the  breath  and  the  pa- 


152  CANCER 

tient  will  complain  that  everything  has  a  char- 
acteristic taste  of  the  odor  mentioned.  If  its 
use  is  pushed  further,  general  depressing 
effects  may  be  observed  on  the  system,  to- 
gether with  an  increased  amount  of  pain, 
which  will  previously  have  been  noticed  to  di- 
minish or  disappear,  and  an  increased  amount 
of  neutral  sulphur  will  make  its  appearance 
in  the  urine.  Our  experience,  so  far,  has  not 
always  borne  out  just  the  results  which  might 
be  anticipated,  as  mentioned  above;  enough 
sulphur  examinations  associated  with  selenium 
have  not  been  made  by  us  to  enable  us  to 
make  a  positive  statement  as  to  its  effect  in 
that  respect,  but  in  certain  cases  in  which  we 
have  made  these  examinations  the  above  con- 
tention has  been  borne  out.  In  all  cases  in 
which  we  have  administered  selenium,  irre- 
spective of  the  preparation  of  selenium  which 
has  been  given,  there  has  been  a  diminution 
of  pain  following  its  administration  so  marked 
as  to  lead  us  to  believe  that  it  does  have  a 
direct  action  in  that  respect.  Also,  while  we 
have  seen  such  toxic  effects  as  a  garlicky  taste 
follow  the  prolonged  administration  of  the 
colloidal  selenium,  we  have  never  seen  any 
bad  after-effects,  while  we  have  seen  gratify- 
ing results  so  marked  as  to  make  us  believe 


SELENIUM  AND  TELLURIUM  1 53 

that  it  does  have,  in  certain  cases  at  least,  a 
marked  constitutional  effect  for  the  better. 
At  the  same  time  we  have  no  desire  to  recom- 
mend it  as  a  cure-all,  but  within  the  lines  fol- 
lowing the  laws  under  which  its  effects  ap- 
pear, benefit  will  undoubtedly  follow  its 
administration. 

We  have  used  it  previous  to  operation,  in 
a  far  advanced  case  that  refused  operation, 
without  any  apparent  result;  but  its  continu- 
ous use  following  operation,  consent  having 
been  given  later,  in  the  same  case,  which 
showed  a  tendency  to  malignancy  to  occur  in 
the  old  scar,  has  been  attended  with  good  re- 
sults, apparently  a  complete  recovery  taking 
place. 

In  another  case  following  operation  and 
radium  for  malignant  growth  in  an  extensive 
area,  recurrence  has  taken  place,  its  use  has 
apparently  in  some  way  arrested  such  prog- 
ress and  restored  the  individual  to  a  com- 
paratively healthful  state. 

In  a  far  advanced  case,  such  as  reinvasion 
following  the  operation  for  the  removal  of 
both  breasts,  and  extensive  involvement  of  the 
chest  wall  at  the  back,  it  has  apparently  re- 
tarded further  progress.  In  such  conditions 
as  inoperable  cancer  of  the  bladder  it  has  been 


154  CANCER 

found  useful  to  relieve  pain  and  for  the  con- 
trol of  hemorrhage,  thereby  making  the  pa- 
tient more  comfortable  and  apparently  re- 
tarding the  progress,  but  without  curing  the 
individual. 

We  have  experimented  with  selenium  com- 
pounds from  three  different  manufacturers. 
The  one  from  which  we  have  obtained  the 
best  results  and  which  we  are  at  present  using 
is  manufactured  by  E.  C.  Steinach,  of  this 
city,  and  can  be  obtained  of  Munsch,  Protz- 
mann  &  Co.,  410  Madison  Avenue,  in  the 
form  of  tablets,  which,  it  is  stated,  contain  one 
and  one-half  milligrams  of  colloidal  selenium, 
with  about  one  grain  each  of  chloride  of  po- 
tassium and  sulphate  of  potassium.  They  also 
prepare  the  solution  of  potassium  seleno-vana- 
date,  as  well  as  some  of  the  salts  of  tellurium. 
Selenium  is  fortunately  an  inexpensive  prod- 
uct to  obtain,  but  the  preparations  should  not, 
we  have  been  informed,  be  manufactured 
from  selenium  that  has  been  heated  to  a  great 
extent,  and  care  should  be  used  to  free  the 
metal  in  the  process  of  manufacture  from  all 
impurities. 

Tellurium,  like  selenium,  has  the  property 
of  oxidation  in  the  animal  organism.  It  be- 
longs to  the  same  group  as  sulphur  and  se- 


SELENIUM  AND  TELLURIUM  1 55 

lenium.  Its  action  is  somewhat  milder,  and 
it  therefore  has  to  be  given  in  much  larger 
doses.  Its  toxic  effects  are  much  less  than  in 
the  case  of  selenium,  but  they  are  harder  to 
detect  after  the  system  is  saturated,  unless  by 
chemical  tests  of  the  urine.  It  is  an  oxidizer, 
the  same  as  selenium,  and  is  recommended  in 
cases  where  the  neutral  sulphur  is  present  to 
a  very  great  extent. 

This  is  a  much  rarer  element  than  selenium. 
The  metallic  tellurium  at  the  present  time 
upon  the  market  varies  anywhere  from  20  per 
cent  to  75  per  cent  to  95  per  cent  balance  im- 
purities; and  while  the  salts  are  more  stable 
than  those  of  selenium,  they  are  more  difficult 
to  prepare,  tellurium  being  a  less  active  ele- 
ment. It  combines  with  the  earthy  elements 
like  potassium,  sodium  lithium,  to  form  solu- 
ble salts,  which  can  be  obtained  in  a  reason- 
ably pure  state. 

Tellurous  acid  salts  have  been  given  in 
five-milligram  doses  three  times  daily.  Per- 
sonally we  have  had  no  experience  with  its 
internal  administration,  but  when  taken  to 
any  considerable  extent  it  sometimes  produces 
a  dermatitis,  which  fact  renders  the  thera- 
peutic use  of  tellurium  valueless.  In  car- 
cinomatous conditions  tellurium  may  be  best 


156  CANCER 

employed  as  telluric  acid,  applied  locally  in 
an  antiseptic  solution.  (See  chapter  on  Anti- 
septics.) 

Every  tumor  ought  to  be  removed  sur- 
gically if  suspected  to  be  malignant.  Inves- 
tigation of  the  urine  as  regards  sulphur  should 
be  made  previous  to  operation.  The  surgical 
removal  of  the  tumor  should  also  be  followed 
by  selenium  administration.  The  success  of 
the  procedure  surgically  and  the  internal 
administration  of  selenium  cannot  be  judged 
until  some  two  or  three  years  following  the 
operation.  However,  if  a  recurrence  follows 
in  the  old  scar  or  as  a  result  of  metastases, 
this  cannot  be  readily  detected  by  a  disturb- 
ance in  the  sulphur  excretion. 


CHAPTER   VI 

Preparations  for  Cleansing,  Deodorizing, 
AND  Disinfecting  Cancerous  Lesions 
OF  THE  Skin 

Practically  all  who  have  been  in  attendance 
on  those  suffering  from  ulcerated  surfaces  of 
the  skin  associated  with  cancer,  if  the  ulcera- 
tion was  of  any  extent,  have  felt  the  need  of 
some  application  that  would  place  the  ulcer- 
ated areas  in  a  more  healthul  condition,  and 
at  the  same  time  disguise  or  remove  the  un- 
pleasant odor  associated  with  them,  a  prepa- 
ration not  intended  to  act  as  an  active 
destructive  agent,  like  arsenous  acid  paste, 
previously  mentioned,  radium.  X-ray,  or 
excision ;  but  for  the  purpose  mentioned  above 
we  recommend  Dakin's  solution  as  prepared 
by  Killian's  formula,  or  the  paste  dichlora- 
mine  T.  The  formulas  for  the  manufacture 
of  both  these  preparations  are  presented  in 
this  chapter.  The  medical  profession  is  in- 
debted to  Dr.  Alexis  Carrel  for  work  done, 
both    abroad    and    at    the    Rockefeller    In- 

157 


158  CANCER 

stitute,  for  popularizing  Dakin's  solution. 
Before  giving  these  formulas  it  may  be  well 
to  review  briefly  what  action  it  is  desired  to 
obtain  by  their  use,  and  the  reasons  for  the 
same. 

Nature  has  two  defenses  against  infection. 
The  first,  the  number  of  antibodies  normally 
present  or  developed;  and  second,  phagocy- 
tosis assisted  by  opsonins.  These  are  the  pre- 
cise periods  to  remove  infection.  The  anti- 
bodies start  in  from  one  to  two  hours  from 
the  period  of  contamination,  up  to  twelve 
hours.  The  phagocytosis  begins  when  the  line 
of  demarcation  has  been  established  between 
healthy  and  diseased  tissue,  and  lasts  for  a 
longer  period  of  time.  The  first  thing  to  be 
done  is  to  remove  the  necrosed  tissue,  because 
it  is  at  this  time  that  antiseptics  find  their 
greatest  usefulness.  The  most  common  anti- 
septic used  is  carbolic  acid  (crude),  intro- 
duced by  Lister.  Its  power  of  asepsis  is  good, 
but  it  also  destroys  tissue. 

In  the  cancerous  ulcerations  the  period  of 
contamination  has  passed  before  the  patient 
comes  under  our  observation.  The  proper 
preparation  to  be  used  is  one  which  contains 
some  of  the  qualities  of  a  germicide  (which 
destroys  micro-organisms),   of  an   antiseptic 


ANTISEPTICS,  ETC.  1 59 

(which  works  against  sepsis),  or  of  a  disin- 
fectant (which  is  used  to  combat  infection, 
or  to  do  away  with  it).  The  antiseptics  are 
divided  into:  (i)  phenolic;  (2)  metallic  salts, 
HgCl2,  HgNOs;  (3)  dyes;  (4)  halogens, 
e.  g.^  iodine,  etc.;  (5)  miscellaneous,  e.  ^., 
hydrogen  peroxide,  alcohol,  etc.  Of  all  these 
the  chlorine  group  has  given  the  greatest 
satisfaction. 

Chlorine  Compounds. — There  are  four 
available  chlorine  compounds,  of  which  two 
at  present  are  widely  employed.  All  of  the 
chlorine  compounds  have  chlorine  in  active 
form,  loosely  bound  and  readily  given  up. 
Attention  is  called  to  the  fact  that  the  prin- 
cipal test  of  chlorine  is  the  liberation  of  iodine 
from  KI.  Some  of  the  formulas  are  as  fol- 
lows: 

r>u^     '      ( chloramines 
Chlorme  4  ^  ,  .     • 

(  hypochlorite 

Chlorine  united  to  N 

N-Cl  N(g 

mono-  di- 

In  studying  the  action  of  hypochlorites 
upon  protein  substances,  H  was  replaced  by 
chlorine,  forming  chloramino-acids.     Chlor- 


l6o  CANCER 

amino-acids  are  antiseptics.  The  principal 
hypochlorite  preparations  are  Dakin's  solu- 
tion and  eusol.  To  prepare  eusol,  bleaching 
powder  and  boric  acid  in  equal  parts  are 
taken,  water  added,  and  filtered.  These  solu- 
tions make  an  alkaline  mixture.  Ca(OH)2 
and  carbonate  and  Ca(OCl)2  and  a  little 
HCIO.  These  are  very  easily  prepared. 
Formula  for  eusol : 

1 2.5  gms.  Ca(OCl)2 
12.5  gms.  boric  acid 
1,000  c.c.  water. 

Dakin's  solution  must  be  neutral;  0.5  per 
cent  NaOCl.  When  used  in  a  stronger  solu- 
tion causes  irritation,  and  below  this  is  in- 
efficient.    Methods  of  making  solution: 

1.  NaoC03  +  CI2  (gas). 

2.  Ca(OCl)2  +  Na2C03  +  NaHCOs. 

3.  NaOCl  +  (from   Ca(OCl)2   with 

Na2C03)   boric  acid. 

The  last  of  these  three  is  the  best. 

Boric  acid  as  a  polybasic  acid  is  more  effi- 
cient in  the  neutralization  of  antiseptics  than 
neutralization  with  sodium  carbonate.  In  the 
preparation  of  an  antiseptic  we  must  get  our 


ANTISEPTICS,  ETC.  l6l 

measure  at  a  point  where  it  gives  a  red  color 
with  alcoholic  phenolphthalein,  and  no  color 
with  solid  phenolphthalein.  If  it  becomes 
too  alkaline  it  destroys  not  only  necrosed  tis- 
sue, but  also  healthy  tissue,  and  consequently 
hampers  the  neighboring  tissue  cells  in  their 
protective  action  against  the  invasion  of  any 
infection.  On  the  other  hand,  if  it  is  not  suf- 
ficiently alkaline,  its  keeping  properties  are 
so  very  poor  that  it  deteriorates  two  hours 
after  preparation. 

In  the  action  of  antiseptics  on  necrosed  tis- 
sue the  chlorine  combines  with  the  nitrogen, 
forming  chloramino-acids.  Consequently  the 
mixture  takes  on  an  acid  reaction,  but  the 
alkalinity  of  the  antiseptic  will  neutralize  this 
acid.  In  certain  types  of  infection,  and  this  is 
particularly  true  of  those  concerned  in  can- 
cer, the  mixture  is  more  likely  to  become 
alkaline,  and  we  must  therefore  have  some 
compound  in  the  antiseptic  capable  of  neu- 
tralizing that  alkalinity.  For  that  purpose 
we  have  chosen  as  a  substitute  for  boric  acid, 
telluric  acid.  Telluric  acid  belongs  to  the 
same  chemical  group  as  boric  acid,  and  it  is 
likewise  a  polybasic  acid.  It  therefore,  like 
the  phosphates  and  carbonates  of  the  blood, 
has   a   true   buffer   action,   covering   a  wide 


1 62  CANCER 

range  of  hydrogen  ion  concentration.  More- 
over, telluric  acid,  or  the  salts  of  telluric  acid, 
when  used  in  moderate  quantities,  stimulate 
epithelial  cells  in  their  protective  action 
against  infection  or  the  invasion  of  malignant 
cells.  For  the  making  of  the  antiseptic  we 
follow  the  formula  for  Dakin's  solution,  where 
the  sodium  hypochlorite  is  prepared  from 
chlorinated  lime  and  sodium  carbonate.  This 
is  rendered  alkaline  to  phenolphthalein,  and 
then  telluric  acid  is  added  until  the  mixture 
gives  no  color  with  solid  phenolphthalein. 
This  requires  very  little  telluric  acid,  and  the 
keeping  properties  of  the  mixture  are  very 
good. 


Application  of  the  Antiseptic 

To  obtain  the  best  results  with  the  antisep- 
tic, the  wound  is  saturated  every  two  hours, 
and  between  applications  smears  are  made  of 
the  exudate.  The  smears  are  stained  with 
Loeffler's  menthylene  blue,  and  the  bacteria 
to  a  high-power  field  counted.  The  average 
of  some  ten  fields  is  taken  as  a  safe  indication 
of  the  degree  of  infection.  The  antiseptic  is 
applied  until  the  number  of  bacteria  is  greatly 
diminished,  that  is,  to  one  or  two  to  a  high- 


ANTISEPTICS,  ETC.  1 63 

power  field.  It  will  be  noted  at  this  period 
that  the  amount  of  exudate  is  very  small.  The 
wound,  moreover,  has  taken  on  a  healthier 
appearance  and  the  invasion  of  neighboring 
parts  has  stopped.  In  some  cases,  as,  for  in- 
stance, in  carcinoma  of  the  breast,  the  appli- 
cation of  the  antiseptic  continually  may  cause 
irritation.  In  that  case  it  is  wise  to  dilute  it 
with  an  equal  quantity  of  distilled  water  and 
apply  more  frequently.  It  is  also  to  be 
recommended  that  if  the  antiseptic  is  to  be 
kept  for  any  length  of  time,  that  potassium 
permanganate  be  added,  to  the  amount  of  5 
milligrams  to  a  liter,  to  add  to  its  keeping 
qualities.  If  a  paste  is  desired,  and  in  some 
cases,  as  in  epitheliomata  of  the  face,  where 
constant  irrigation  without  injury  to  other 
structures,  as  the  eye,  is  impossible,  the  most 
valuable  paste  is  that  prepared  by  adding  to 
sodium  stearate  dichloramine  T,  plus  sodium 
arsenite.  Dichloramine  T  may  be  made  from 
sodium  sulphonamide  by  adding  hypochlorous 
acid,  or  preferably  by  adding  to  the  sulpho- 
namide sodium  hypochlorite  and  heating  until 
the  solution  is  obtained,  then  adding  acetic 
acid.  A  white  crystalline  precipitate  is  ob- 
tained, and  this  is  taken  up  in  the  stearate  as 
a  vehicle  and  the  arsenic  is  added.    One  gram 


164  CANCER 

of  the  arsenite  is  added  to  100  grams  of  the 
dichloramine  paste.  One  application  of  this 
paste  in  twenty-four  hours  is  sufScient.  Un- 
less some  unforeseen  condition  should  prevent, 
when  using  it,  the  Dakin's  solution  should  be 
kept  constantly  applied  by  means  of  the  tube, 
placed  in  the  dressing  in  the  manner  in  which 
it  is  ordinarily  used.  After  the  ulceration  has 
been  put  into  a  healthy  state,  as  mentioned 
above,  then  the  wet  dressing  can  be  removed, 
and  probably  the  washing  off  of  the  ulcera- 
tion once  a  day  through  a  glass  syringe  will 
be  enough  to  keep  it  in  a  healthy  state.  Par- 
ticularly in  cold  weather,  it  may  be  enough 
for  such  conditions  as  cancer  of  the  breast, 
when  it  is  not  advisable  or  convenient  for  the 
patient  to  be  confined  to  bed,  to  apply  the 
paste  instead  of  the  solution  once  a  day  after 
the  ulceration  has  reached  a  healthy  state. 
In  summer,  on  account  of  the  tendency  of  the 
stearate  to  decompose,  the  paste  had  better 
not  be  applied  over  any  extensive  surfaces. 
The  disagreeable  odor  will  be  disguised  by 
the  chlorine  present  in  the  Dakin's  solution, 
and  after  the  ulceration  has  reached  a  more 
healthy  state,  will  cease  of  its  own  accord  to 
be  present,  as  the  conditions  which  give  rise 
to  it  will  have  been  removed. 


ANTISEPTICS^  ETC.  1 65 

The  above  two  preparations  we  recommend 
more  highly  than  any  other  as  the  best  local 
applications  for  cleansing,  deodorizing,  and 
disinfecting  these  ulcerated  cancerous  sur- 
faces, but  even  where  their  action  is  attended 
with  pleasing  results,  too  much  reliance  should 
not  be  placed  on  them  alone,  but  every  en- 
deavor should  be  made,  through  the  internal 
administration  of  selenium  or  whatever  me- 
dicinal preparations  may  be  used,  to  take 
advantage  of  this  opportunity  to  combat  the 
disease  by  their  internal  administration  and  to 
use  every  other  climatic  and  hygienic  meas- 
ure which  is  at  the  command  of  the  attendant. 

The  formula  for  eusol  is  given  in  this  chap- 
ter because  it  is  easier  to  prepare  than  Dakin's 
solution  and  can  be  used  in  place  of  it  when 
the  latter  is  unobtainable.  Where  it  is  im- 
practicable or  impossible  to  employ  all  of  the 
technique  which  we  recommend  as  associates 
with  the  application  of  Dakin's  solution,  such 
as  the  examination  of  the  smears  under  a  high- 
power  microscope,  the  attendant  can  use  the 
preparations  recommended,  if  found  to  be 
of  benefit,  according  to  his  best  judgment. 
Naturally  it  is  easier  to  use  these  preparations 
in  institutions  which  are  properly  equipped 
for  pathological  and  chemical  work.    Unfor- 


1 66  CANCER 

tunately,  even  to-day  not  infrequently  institu- 
tions, otherwise  well  equipped  for  the  care 
of  individuals  suffering  from  malignant  dis- 
ease, are  very  poorly  fitted  out  in  the  above 
two  particulars.  Every  two  hours  is  sufficient 
to  apply  the  solution  through  the  tube.  In 
this  manner  the  dressing  of  gauze  is  kept  con- 
stantly wet. 

In  cases  where,  in  spite  of  all  possible  care, 
the  application  of  Dakin's  solution  or  the  paste' 
is  found  to  disagree,  there  are,  as  previously 
mentioned,  a  great  variety  of  antiseptic  solu- 
tions or  unirritating  ointments  that  may  be 
applied  for  the  same  purpose.  Our  experi- 
ence has  been  that  ordinarily  the  best  results 
are  obtained  by  the  weak  and  less  irritating 
germicides;  solutions  of  aluminum  acetate  or 
lead  and  opium  wash  are  sometimes  useful. 
Boric  ointment  or  an  ointment  which  is  at 
present  on  the  market  which  contains  tellu- 
rium and  selenium,  under  the  name  of  Un- 
guentum  Sel-Van-Sen,  may  be  tried  around 
the  edges  for  the  purpose  of  preventing  fur- 
ther infection  and  with  the  idea  of  absorption 
of  the  selenium  by  the  system. 

The  Dakin  solution,  modified  according  to 
the  Killian  formula,  either  plain  or  diluted, 
can  be  used,  and  its  effects  observed,  on  can- 


ANTISEPTICS,  ETC.  167 

cerous  ulcerations  on  mucous  membranes, 
either  as  a  douche  or  a  wash.  Great  care 
should  be  used,  however,  in  using  this  solu- 
tion around  the  face  where  there  is  an  oppor- 
tunity of  its  being  inhaled,  as  the  chlorine 
might  prove  irritating  to  the  lungs. 


CHAPTER   VII 

General  Considerations 

As  has  been  stated,  this  little  work  is  the 
combined  efforts  of  a  chemist  and  surgeon 
working  together,  both  of  whom  have  studied 
the  cancer  problem  from  their  respective 
standpoints  for  several  years.  Some  of  the 
conclusions  which  have  been  presented  are 
the  result  of  the  work  that  both  of  them  have 
done,  in  association  with  homes  for  the  relief 
of  incurables,  or  as  a  result  of  observations 
made  in  hospitals,  in  the  wards  of  which  the 
most  far  advanced  cases  are  apt  to  present 
themselves,  being  filled  with  the  most  de- 
pendent of  all  of  a  large  city's  population. 
Therefore,  to  a  very  great  extent,  the  conclu- 
sions are  founded  on  observations  made  on 
the  most  difficult  cases.  This  work  has  in- 
tensified our  belief  in  the  value  of  what  can 
be  done  for  the  relief  of,  or  at  least  the  re- 
tardation of  the  advance  of  the  processes  in 
earlier  cases,  when  an  accurate  diagnosis  has 
once  been  made,  by  the  use  of  measures  often 

i68 


GENERAL  CONSIDERATIONS  1 69 

neglected,  which  we  have  at  the  present  time, 
while  expecting  the  discovery  of  some  new 
remedial  measure,  possibly  a  serum,  which 
will  cure  this  condition  in  a  semi-miraculous 
manner.  We  have  learned  not  to  expect  too 
much  from  such  preparations  as  tuberculin 
for  tuberculosis,  or  from  mercury  or  salvarsan 
in  syphilis,  although  the  use  of  these  two  lat- 
ter have  been  of  invaluable  aid ;  and  we  should 
not  expect  too  much  from  any  sudden  cure  for 
cancer. 

Just  the  same,  in  carcinoma  we  predicate 
that  even  now  astonishingly  good  results  can 
be  obtained  from  the  careful  and  persistent 
use  of  measures  which  we  have  at  our  com- 
mand. The  history  taking  is  of  the  very 
greatest  importance.  In  any  case  where  there 
is  the  least  ground  to  suspect  malignant 
growth,  in  taking  the  history  due  regard  must 
be  paid  to  the  fact  that  slow  mental  reaction 
follows  questioning  in  many  cases.  It  may  be 
necessary  to  ask  the  same  question  over  and 
over  again,  particularly  concerning  the  cause 
of  death  of  collateral  relations  of  the  indi- 
vidual who  is  being  examined.  Clinically 
such  a  condition  has  been  observed  by  us  as 
a  marked  increase  of  neutral  sulphur  in  an 
individual  of  a  distinguished  family,  where  a 


I  JO  CANCER 

careful  family  history  had  been  kept  for  one 
hundred  years,  and  in  whose  family  is  re- 
corded the  death  of  eleven  persons  from  can- 
cer, the  common  ancestor  being  the  patient's 
grandfather.  In  such  individuals  a  careful 
history- recording  will  in  time  prove  not  only 
of  aid  in  the  diagnosis  of  any  individual  case, 
but  continued  careful  history-taking  will 
eventually  help  clear  up  some  of  the  points  in 
connection  with  heredity  in  this  disease. 
Much  still  exists  that  can  be  accomplished  in 
the  future  by  observations  of  the  records  of 
the  various  countries,  as  shown  by  the  report 
of  the  health  officers,  and  the  discovery  of 
those  regions  where  cancer  does  or  does  not 
exist.  Our  observations  so  far  are  that 
neither  climatic  conditions  nor  racial  charac- 
teristics have  any  effect  outside  of  the  influ- 
ence they  may  have  on  general  hygienic  con- 
ditions, but  that  heredity  is  a  powerful  factor 
which  is  always  to  be  considered.  Life  in  the 
open  air,  particularly  for  individuals  in  whom 
cancer  is  diagnosed  in  its  earlier  stages,  can- 
not be  too  highly  commended.  Contrary  to 
the  opinion  of  many,  we  regard  the  question 
of  diet  of  secondary  importance,  providing 
digestible  food  in  sufficient  quantities  is  ob- 
tainable.   The  diet  can  be  modified  somewhat 


GENERAL  CONSIDERATIONS  171 

according  to  the  exigencies  in  each  individual 
case. 

Everything  should  be  done  to  cheer,  en- 
courage, and  calm  the  mental  state  of  unfor- 
tunate individuals  so  affected,  and  all  meas- 
ures of  a  material,  social,  and  spiritual  nature 
that  are  practical  should  be  adopted  for  this 
purpose. 

So  far  as  we  are  able  to  ascertain,  cancer 
differs  from  syphilis,  in  the  earlier  stages  of 
the  latter  disease,  in  the  fact  that  it  is  not 
contagious,  and  probably  in  that  respect  from 
tuberculosis  also. 

It  is  a  question  whether  the  somewhat  com- 
plex question  of  cancer  and  marriage  should 
be  discussed  in  a  work  of  this  description, 
which  is  intended  to  be  of  a  scientific  char- 
acter. It  is  desired  to  touch  as  little  as  pos- 
sible on  either  philosophical  or  religious 
grounds.  The  three,  however,  are  sometimes 
so  dependent  on  one  another  that  it  is  impos- 
sible to  discuss  them  separately.  Naturally, 
individuals  of  either  sex  with  a  malignant 
growth  clearly  demonstrable  will  refrain  from 
marriage.  It  may  be  expected  that  an  increas- 
ing number  of  individuals  will  be  discovered 
as  sufferers  from  a  pre-cancerous  state,  either 
by  the  use  of  methods  for  diagnosis  which  are 


172  CANCER 

just  now  commencing  to  be  applied,  or  by 
increasing  refinements  in  that  direction  from 
future  discoveries.  These  people  can  prob- 
ably be  cured  of  a  condition,  when  once  it  is 
recognized,  by  the  careful  adoption  of  every 
hygienic  or  medicinal  measure  calculated  to 
increase  and  sustain  proper  tissue  metamor- 
phosis for  at  least  two  years.  They  can  at  least 
be  relatively  cured  to  the  extent  that  indi- 
viduals are  relatively  cured  of  other  similar 
conditions,  such  as  tuberculosis;  and  they 
probably  will  not  transmit,  to  the  extent  they 
have  received  it,  the  tendency  toward  the  de- 
velopment of  malignant  neoplasm.  It  is  fair 
to  hope  that  it  is  in  accord  with  the  laws  of 
heredity  (and  apparently  it  is  to  the  extent 
known  to  us)  that  through  these  measures  it 
can  eventually  be  bred  out  of  the  system,  just 
as  now,  if  we  can  go  by  the  records  that  are 
already  being  presented  to  us,  it  is  being  bred 
in;  and  that  in  the  future,  and  probably  not 
far  distant  future,  its  frequency  of  occurrence 
will  be  very  materially  diminished. 


^CUGv. 


>-vr-H- 


